Task 6: Sequence-based mutation analysis

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Revision as of 10:10, 27 June 2011 by Meier (talk | contribs) (Execution)

Task description

A detailed task description can be found here.

Mutation selection

We selected the following ten mutations:

  • I65T
  • R71H
  • R158Q
  • R261Q
  • T266A
  • P275S
  • T278N
  • P281L
  • G312D
  • R408W

5 of these mutations are associated with our disease phenylketonuria the other 5 not. The 5 disease causing mutations are the most frequent missense/nonsense mutations of people who suffer from phenylketonuria. These numbers were taken from pahDB. However, at this point we are not going to tell which of these are the associated and which are not. We are going to lift this "secret" after our sequence based mutation analysis in order to validate our in silico generated predictions.

To keep our association secret we encrypted the file which contains the disease association for each mutation with the following linux command: "vim -x selected_mutations_and_association.txt"

The encrypted output is as follows:

Encrypted img.png


The decryption can be only performed with the correct password.

Physicochemical properties and changes

For the annotation of the physicochemical properties of our amino acids we used the following venn diagram from [1]:

Aa venn diagram.png

Additionally to this we used also the table of this Wikipedia page as a reference.

I65T

I: aliphatic, hydrophob, large, unpolar, neutral
T: small, hydrophob, polar, neutral

R71H

R: polar, aliphatic, positive charged, hydrophob, large, neutral
H: positive charged, polar, aromatic, hydrophob, basic

R158Q

R: polar, aliphatic, positive charged, hydrophob, large, neutral

Q: polar, aliphatic, hydrophob, neutral

R261Q

R: polar, aliphatic, positive charged, hydrophob, large, neutral
Q: polar, aliphatic, hydrophob, neutral

T266A

T: small, hydrophob, polar, neutral

A: tiny, hydrophobic, nonpolar, neutral

P275S

P: small, proline, nonpolar, neutral

S: tiny, polar, neutral

T278N

T: small, hydrophob, polar, neutral

N: small, polar, neutral

P281L

P: small, proline, nonpolar, neutral

L: hydrophobic, aliphatic, nonpolar, neutral

G312D

G: very small, unpolar, neutral
D: polar, small, negative charged, acidic

R408W

R: polar, aliphatic, positive charged, hydrophob, large, neutral
W: polar, aromatic, large, hydrophob, neutral

Visualization of the changed Amino Acid

We used the structure 1J8U to visualize our mutations with Pymol. This structure is only solved from residue 118 to residue 424. Hence we could not visualize the mutations at position 65 and 71.

I65T

Was not included in the used structure.

R71H

Was not included in the used structure.

R158Q

R156Q.png

R261Q

Figure .... Visualization of the mutated residue Q (white) versus the wildtype residue R (green) in the structure of PAH.

T266A

T266A.png

P275S

P275S.png

T278N

T278N.png

P281L

P281L.png

G312D

Figure .... Visualization of the wildtype residue G (blue) in the structure of PAH. Figure .... Visualization of the mutated residue D (white) in the structure of PAH.

R408W

Figure .... Visualization of the mutated residue W (white) versus the wildtype residue R (green) in the structure of PAH.

Mutations compared to BLOSUM62, PAM(1/250), PSSM and conservation of MSA with all mammalian homologous

BLOSUM 62 matrix

BLOSUM 62 Matrix
BLOSUM62 BCKDHA.gif
The BLOSUM 62 was calculated from blocks of clusters with a sequence identity of 62%. A positive score is given to the more likely substitutions while a negative score is given to the less likely substitutions. Source: [2] Disclaimer: This file is redistributed from Wikimedia and copyrighted under the Creative Commons licence.

PAM 1/250 matrix

We took the values for our PAM1 and PAM 250 matrix from this page.

PAM1 Matrix

A R N D C Q E G H I L K M F P S T W Y V
A 9867 2 9 10 3 8 17 21 2 6 4 2 6 2 22 35 32 0 2 18
R 1 9913 1 0 1 10 0 0 10 3 1 19 4 1 4 6 1 8 0 1
N 4 1 9822 36 0 4 6 6 21 3 1 13 0 1 2 20 9 1 4 1
D 6 0 42 9859 0 6 53 6 4 1 0 3 0 0 1 5 3 0 0 1
C 1 1 0 0 9973 0 0 0 1 1 0 0 0 0 1 5 1 0 3 2
Q 3 9 4 5 0 9876 27 1 23 1 3 6 4 0 6 2 2 0 0 1
E 10 0 7 56 0 35 9865 4 2 3 1 4 1 0 3 4 2 0 1 2
G 21 1 12 11 1 3 7 9935 1 0 1 2 1 1 3 21 3 0 0 5
H 1 8 18 3 1 20 1 0 9912 0 1 1 0 2 3 1 1 1 4 1
I 2 2 3 1 2 1 2 0 0 9872 9 2 12 7 0 1 7 0 1 33
L 3 1 3 0 0 6 1 1 4 22 9947 2 45 13 3 1 3 4 2 15
K 2 37 25 6 0 12 7 2 2 4 1 9926 20 0 3 8 11 0 1 1
M 1 1 0 0 0 2 0 0 0 5 8 4 9874 1 0 1 2 0 0 4
F 1 1 1 0 0 0 0 1 2 8 6 0 4 9946 0 2 1 3 28 0
P 13 5 2 1 1 8 3 2 5 1 2 2 1 1 9926 12 4 0 0 2
S 28 11 34 7 11 4 6 16 2 2 1 7 4 3 17 9840 38 5 2 2
T 22 2 13 4 1 3 2 2 1 11 2 8 6 1 5 32 9871 0 2 9
W 0 2 0 0 0 0 0 0 0 0 0 0 0 1 0 1 0 9976 1 0
Y 1 0 3 0 3 0 1 0 4 1 1 0 0 21 0 1 1 2 9945 1
V 13 2 1 1 3 2 2 3 3 57 11 1 17 1 3 2 10 0 2 9901

PAM250 Matrix

A R N D C Q E G H I L K M F P S T W Y V
A 13 6 9 9 5 8 9 12 6 8 6 7 7 4 11 11 11 2 4 9
R 3 17 4 3 2 5 3 2 6 3 2 9 4 1 4 4 3 7 2 2
N 4 4 6 7 2 5 6 4 6 3 2 5 3 2 4 5 4 2 3 3
D 5 4 8 11 1 7 10 5 6 3 2 5 3 1 4 5 5 1 2 3
C 2 1 1 1 52 1 1 2 2 2 1 1 1 1 2 3 2 1 4 2
Q 3 5 5 6 1 10 7 3 7 2 3 5 3 1 4 3 3 1 2 3
E 5 4 7 11 1 9 12 5 6 3 2 5 3 1 4 5 5 1 2 3
G 12 5 10 10 4 7 9 27 5 5 4 6 5 3 8 11 9 2 3 7
H 2 5 5 4 2 7 4 2 15 2 2 3 2 2 3 3 2 2 3 2
I 3 2 2 2 2 2 2 2 2 10 6 2 6 5 2 3 4 1 3 9
L 6 4 4 3 2 6 4 3 5 15 34 4 20 13 5 4 6 6 7 13
K 6 18 10 8 2 10 8 5 8 5 4 24 9 2 6 8 8 4 3 5
M 1 1 1 1 0 1 1 1 1 2 3 2 6 2 1 1 1 1 1 2
F 2 1 2 1 1 1 1 1 3 5 6 1 4 32 1 2 2 4 20 3
P 7 5 5 4 3 5 4 5 5 3 3 4 3 2 20 6 5 1 2 4
S 9 6 8 7 7 6 7 9 6 5 4 7 5 3 9 10 9 4 4 6
T 8 5 6 6 4 5 5 6 4 6 4 6 5 3 6 8 11 2 3 6
W 0 2 0 0 0 0 0 0 1 0 1 0 0 1 0 1 0 55 1 0
Y 1 1 2 1 3 1 1 1 3 2 2 1 2 15 1 2 2 3 31 2
V 7 4 4 4 4 4 4 4 5 4 15 10 4 10 5 5 5 72 4 17

PSSM

The readable PSSM file of PSI-Blast can be generated by the -Q option:
blastpgp -d '/data/nr/nr' -i './reference.fasta' -o './reference_psi_e10E-6_i5.blast' -h 10E-6 -j 5 -Q reference_i5_e10E-6.txt

Position AA A R N D C Q E G H I L K M F P S T W Y V A R N D C Q E G H I L K M F P S T W Y V
1 M -3 -4 -5 -5 -3 -3 -4 -5 -4 0 5 -4 7 -1 -5 -4 -3 -3 -3 -1 0 0 0 0 0 0 0 0 0 0 66 0 34 0 0 0 0 0 0 0 1.13 0.65
2 S 4 -3 1 -3 -3 -3 -2 1 1 -4 -4 -3 -3 -5 -3 3 -1 -5 -4 -3 46 0 8 0 0 0 2 11 4 0 0 0 0 0 0 28 1 0 0 0 0.75 0.91
3 T 2 -3 2 -3 -4 -3 -3 2 2 -5 -5 -3 -4 -4 -2 4 1 3 -3 -4 19 0 9 0 0 0 0 13 6 0 0 0 0 0 1 39 9 5 0 0 0.68 1.04
4 A 2 -3 0 -1 -4 -3 -3 -1 -4 0 1 1 -2 -4 -4 2 -2 -5 -4 3 18 0 5 3 0 0 1 4 0 4 14 9 0 0 0 17 1 0 0 25 0.35 1.10
5 V -1 -5 -4 -5 3 -1 -3 -5 -5 5 0 -4 0 -3 -3 0 2 -5 -4 3 4 0 0 0 5 3 1 0 0 37 6 0 1 0 1 6 16 0 0 18 0.67 1.15
6 L 4 -1 -4 -2 -4 1 0 -2 -4 0 2 2 -2 -3 -4 -2 -3 -5 0 -1 33 3 0 2 0 7 6 2 0 5 20 13 0 1 0 1 0 0 3 4 0.39 1.19
7 E -2 -1 3 3 -6 0 5 -2 -3 -3 -5 0 -5 -6 -1 -1 -3 -6 -5 -5 3 3 17 17 0 2 42 2 0 2 0 5 0 0 2 4 1 0 0 0 0.86 1.21
8 N -3 1 4 4 -2 -3 -1 -1 0 -2 -5 1 -3 -5 0 2 -2 -6 -4 -5 0 9 24 24 1 0 2 4 2 3 0 7 1 0 5 15 1 0 0 0 0.65 1.26
9 P 1 -3 -1 -4 -4 -4 -4 -2 -1 4 -3 -1 -3 -2 5 0 -2 -5 1 -2 15 1 3 0 0 0 0 3 2 29 0 4 0 1 26 9 1 0 6 0 0.67 1.28
10 G 1 -2 1 -2 -5 0 3 2 0 -3 -1 -2 -4 -5 1 1 -1 -5 -3 -3 10 1 6 1 0 4 24 17 2 1 6 1 0 0 7 11 4 0 1 2 0.36 1.25
11 L -1 -4 2 4 -5 -3 0 -3 -4 -2 3 -3 -3 -2 -2 1 -2 -5 -1 -3 4 0 10 26 0 0 4 1 0 2 34 1 0 1 2 10 2 0 2 0 0.54 1.30
12 G 0 0 2 0 -5 0 1 2 1 -5 -4 0 -4 -5 -3 1 3 -5 -2 -3 8 5 11 6 0 4 11 13 3 0 1 6 0 0 1 10 19 0 1 1 0.35 1.31
13 R -2 3 0 -3 -5 2 3 -4 -3 -5 -3 2 -4 -5 4 1 1 -6 -5 -4 2 17 4 0 0 8 17 0 0 0 3 11 0 0 18 12 7 0 0 1 0.58 1.34
14 K -3 1 4 1 -4 1 2 -4 1 3 -3 2 -4 -2 -4 1 -2 -5 -2 -2 1 8 18 7 0 7 14 0 3 16 1 11 0 2 0 10 1 0 1 2 0.42 1.36
15 L -3 -3 4 0 -5 -1 3 -1 -2 1 1 -2 -3 4 -5 -2 -3 -4 -2 -3 1 1 19 3 0 2 23 6 0 10 14 2 0 16 0 2 0 0 1 0 0.49 1.33
16 S -3 -3 2 4 -5 -1 0 -4 -1 -1 -1 0 0 -1 -2 2 1 -5 -1 1 0 0 10 23 0 2 6 0 1 3 6 6 2 2 2 13 10 0 2 10 0.35 1.34
17 D -3 0 2 4 -5 -2 1 -1 0 0 -3 0 -1 -3 -4 -1 3 -5 -2 0 1 6 10 23 0 1 8 4 3 5 2 5 2 1 0 3 18 0 1 8 0.39 1.33
18 F -1 3 -4 -3 -3 -2 1 -1 1 -1 1 -1 -3 3 1 -1 -2 -4 0 -1 6 20 0 1 1 1 10 5 4 4 15 3 0 11 7 6 1 0 3 3 0.26 1.31
19 G -1 -3 3 1 -5 0 -3 3 0 -4 -2 -2 0 5 -5 -1 -2 -4 -3 -4 4 1 16 8 0 4 1 25 2 1 4 2 3 22 0 3 2 0 0 1 0.56 1.34
20 Q -3 2 5 0 -5 1 0 -2 -1 -1 2 2 -3 -1 -4 -3 -3 -5 -4 -2 1 10 28 5 0 5 5 2 1 4 18 13 0 3 1 0 0 0 0 3 0.48 1.37
21 E 0 -2 -1 1 -4 0 3 -3 -3 0 -3 1 -3 1 -4 1 1 -5 -1 1 6 1 3 7 0 3 21 2 0 6 1 10 0 6 0 10 10 0 2 11 0.27 1.35
22 T 1 -2 -1 -2 -3 -3 -2 1 -4 2 -1 -1 -2 -3 -3 1 4 -4 -3 0 11 1 3 2 0 0 2 11 0 15 4 3 1 1 1 11 26 0 1 7 0.36 1.30
23 S 0 3 -1 0 -4 -2 -2 1 -3 1 -2 -1 -3 -3 -2 3 -1 -4 -4 -1 8 16 3 5 0 1 1 12 0 8 4 4 0 1 2 28 2 0 0 4 0.35 1.28
24 Y -2 -1 -2 -2 -2 0 2 -3 0 1 -2 0 -2 5 -4 -1 -3 -2 5 -2 3 3 1 3 1 4 13 2 2 8 2 6 1 23 0 4 1 0 20 2 0.55 1.30
25 I -2 -1 -1 -2 -3 1 -1 -3 1 3 1 0 -1 -2 0 1 -1 -5 -3 2 3 3 4 3 1 6 3 2 4 17 15 6 1 1 5 10 4 0 1 14 0.19 1.31
26 E 0 -2 -1 1 -4 0 3 -3 -3 -3 -3 2 -1 1 1 0 -3 -2 -4 1 8 2 3 8 0 4 21 1 0 1 2 15 1 6 7 8 1 1 0 11 0.30 1.33
27 D -2 0 0 3 -2 -1 4 -3 -2 0 -3 -1 -3 -3 1 0 0 -5 -4 0 3 5 4 16 1 1 27 2 1 6 3 4 0 1 8 6 6 0 0 6 0.38 1.33
28 N 1 -3 3 2 -5 -1 3 2 1 -5 -4 0 -4 -5 1 0 -1 -5 -4 -2 12 1 12 10 0 2 18 17 4 0 2 5 0 0 7 5 3 0 0 3 0.39 1.33
29 C -1 1 0 -1 2 -1 2 -4 1 -1 -3 2 -3 0 4 0 -2 -2 -4 0 5 8 4 3 4 2 13 1 4 4 1 12 0 5 17 7 2 1 0 7 0.30 1.33
30 N -1 -2 3 3 -3 0 0 -3 0 -4 -4 0 -3 -4 -3 3 3 -5 -3 -3 5 2 12 16 0 4 6 1 3 0 1 5 1 1 1 26 16 0 1 1 0.51 1.33
31 Q -1 -2 0 -1 -4 0 1 5 -3 0 -4 -2 -3 -4 -1 0 -2 -2 0 -1 5 1 4 2 0 4 11 44 0 7 1 2 0 0 3 6 1 0 4 4 0.59 1.28
32 N 0 2 3 2 -1 -1 -1 -2 1 -2 -3 3 -2 -5 0 0 -2 -6 -4 0 6 12 15 13 1 2 2 3 3 2 1 19 1 0 5 6 1 0 0 7 0.36 1.33
33 G 1 -3 -1 5 -1 2 0 0 0 -1 -4 0 -2 -4 -4 -1 -2 -5 0 -2 13 1 2 36 1 9 4 8 2 4 0 6 1 0 0 3 1 0 4 3 0.54 1.28
34 A -2 3 0 -3 -1 0 0 -4 -3 -2 -1 5 -2 -5 -4 -1 0 -5 -4 -1 2 17 5 0 1 4 6 1 0 2 7 39 1 0 0 5 6 0 0 5 0.62 1.31
35 I 1 -4 -3 -4 -4 -1 -3 -4 -4 2 0 -2 1 0 -4 -1 6 -5 -4 0 10 0 1 0 0 3 1 0 0 11 10 2 3 3 0 1 50 0 0 5 0.76 1.33
36 S 2 -3 1 -1 2 -3 -2 -3 -4 -3 -5 -2 -4 -5 -3 5 2 -3 -4 -3 13 1 5 4 4 0 1 0 0 1 0 2 0 0 1 53 12 0 0 1 0.85 1.34
37 L -4 -5 -6 -6 -1 -5 -5 -6 -5 5 4 -5 1 0 -5 -5 -3 -5 -4 3 0 0 0 0 1 0 0 0 0 31 41 0 3 3 0 0 0 0 0 18 1.05 1.36
38 I -1 -2 -4 -5 -2 0 -2 -6 -5 4 3 -4 2 0 -5 -4 -3 -5 -4 3 4 2 1 0 1 4 2 0 0 28 23 0 5 4 0 0 1 0 0 24 0.70 1.36
39 F -3 -5 -6 -6 -1 -5 -6 -6 -5 2 1 -5 1 7 -6 -5 -3 -3 -1 2 1 0 0 0 1 0 0 0 0 10 14 0 3 54 0 0 1 0 0 15 1.28 1.36
40 S 0 1 -3 -3 -2 -2 -2 -2 2 0 -4 -2 -3 -2 -4 5 3 -5 -2 -3 8 6 0 0 1 1 2 2 5 6 0 2 0 1 0 49 15 0 1 1 0.71 1.36
41 L 0 -4 -4 -5 -2 -2 -5 -4 -5 1 4 -4 2 -2 1 -1 1 -5 -4 2 7 0 0 0 1 2 0 1 0 7 42 0 4 1 7 5 10 0 0 12 0.58 1.40
42 K -2 4 1 -1 -3 0 1 -4 2 -4 -4 4 -4 -5 2 0 -1 -6 -4 -3 3 21 8 3 1 3 7 0 5 1 1 25 0 0 9 7 3 0 0 2 0.58 1.39
43 E -3 -1 5 5 -6 -2 2 -4 2 -6 -6 -2 -5 -5 -4 -1 -2 -6 0 -4 1 3 31 36 0 0 11 0 5 0 0 1 0 0 1 3 2 0 4 1 1.06 1.39
44 E -3 3 0 -2 -6 2 3 1 -1 -5 -5 4 -3 -5 -2 -1 -3 -5 1 -3 1 16 4 1 0 9 20 10 1 0 0 24 0 0 2 4 1 0 5 2 0.59 1.40
45 V 1 -4 -5 -5 2 -3 -4 -5 -5 1 -2 -1 3 -2 5 -1 0 -1 -2 3 10 0 0 0 4 1 0 0 0 7 2 3 7 1 28 5 7 1 1 23 0.67 1.38
46 G -2 -4 1 -3 -5 -1 -2 6 -4 -4 -6 -3 -5 -6 0 0 -1 -5 -5 -5 1 0 7 1 0 3 3 69 0 1 0 0 0 0 5 5 4 0 0 0 1.29 1.36
47 A 4 -2 -1 -1 -1 -3 -1 1 -3 -2 -4 -3 -2 0 -1 3 0 -5 -4 -2 40 1 2 3 1 0 4 9 0 2 1 0 1 4 3 23 5 0 0 2 0.57 1.36
48 L -4 -5 -6 -6 -4 -5 -6 -6 -6 0 6 -5 2 0 -6 -5 -4 -4 -4 0 1 0 0 0 0 0 0 0 0 4 83 0 4 2 0 0 0 0 0 6 1.41 1.38
49 A 3 -1 -4 -4 1 -2 -2 -1 3 -2 -2 -1 -2 1 -2 2 -1 -4 4 1 21 3 0 0 3 1 2 3 8 1 3 4 1 5 2 19 2 0 14 9 0.39 1.38
50 K -2 4 2 2 -5 0 2 -4 2 -5 -5 3 1 -5 -4 0 -1 -6 -4 -5 2 24 9 10 0 4 13 0 5 0 0 18 3 0 0 7 3 0 0 0 0.63 1.38
51 V 3 -5 -4 -5 -1 -5 -5 -5 -5 4 2 -5 2 -2 -5 -2 0 -5 -2 2 25 0 1 0 1 0 0 0 0 27 19 0 4 1 0 2 5 0 2 14 0.66 1.39
52 L -2 -5 -6 -6 -1 -5 -6 -4 -6 1 6 -5 0 -1 -6 -5 -4 -4 -2 -1 3 0 0 0 1 0 0 1 0 6 84 0 1 2 0 0 0 0 1 2 1.36 1.39
53 R 1 2 0 0 -3 2 2 -1 -3 -5 -5 4 -2 -6 -4 1 -1 -6 -3 -3 12 9 5 4 0 7 12 3 0 0 0 31 1 0 0 9 2 0 1 2 0.52 1.39
54 L -1 -5 1 -4 -3 -4 -1 -5 -2 3 1 -3 -1 -3 4 -1 0 -3 -1 3 5 0 6 0 0 0 4 0 1 17 12 1 1 0 20 5 5 0 2 21 0.50 1.41
55 F -5 -5 -6 -6 -5 -6 -6 -6 -4 1 1 -5 1 8 -6 -5 -5 -2 1 -2 0 0 0 0 0 0 0 0 0 9 14 1 3 70 0 0 0 0 2 2 1.71 1.41
56 E 2 0 -2 0 -5 2 3 -3 1 -4 -5 3 -4 -4 -2 1 -1 -1 -2 -5 17 4 1 5 0 11 23 1 3 1 0 16 0 1 1 12 2 1 1 0 0.52 1.42
57 E -1 2 1 2 -5 0 3 -4 -3 -2 -3 2 -1 -6 -1 0 2 -6 -5 -4 4 11 7 13 0 3 19 0 0 2 2 14 2 0 3 7 13 0 0 0 0.45 1.41
58 N 0 2 2 -4 -2 -2 -1 -4 7 -5 -2 1 -3 3 -5 -2 -3 -1 3 -5 8 10 10 0 1 1 5 0 26 0 5 8 0 14 0 1 1 1 10 0 0.73 1.41
59 D -3 -1 2 2 -4 0 1 4 4 -6 -6 2 -5 -6 -4 -1 -4 -6 -3 -6 1 3 10 11 0 3 10 32 9 0 0 15 0 0 0 4 0 0 1 0 0.70 1.40
60 V 0 -5 -5 -6 -4 -5 -5 -1 -6 6 -1 -5 -2 -3 -5 -4 -1 -6 -4 4 8 0 0 0 0 0 0 6 0 43 3 0 0 0 0 0 3 0 0 35 1.03 1.41
61 N -3 -1 7 0 0 0 -1 -3 -1 -4 -6 1 -5 -6 -2 2 0 -6 -5 -5 1 3 51 4 2 4 2 1 1 1 0 9 0 0 2 16 4 0 0 0 1.04 1.44
62 L -4 -5 -6 -6 -4 -5 -6 -6 -6 3 5 -5 5 -3 -6 -5 -3 -5 -4 2 0 0 0 0 0 0 0 0 0 18 49 0 17 0 0 0 1 0 0 15 1.16 1.44
63 T -2 -2 -1 -4 3 0 -3 -4 2 0 1 -2 -1 -4 -5 2 5 -5 -2 0 1 1 3 0 6 3 1 1 6 4 13 2 1 0 0 15 36 0 1 6 0.58 1.49
64 H -4 3 -2 -1 -6 0 -1 -5 9 -2 -4 2 -2 -2 -5 -3 -4 -1 -1 -5 0 14 1 4 0 4 4 0 52 3 1 13 1 2 0 1 0 1 1 0 1.43 1.49
65 I -4 -6 -6 -6 -4 -6 -6 -7 -6 6 2 -6 0 1 -6 -5 -4 -5 -4 3 0 0 0 0 0 0 0 0 0 58 21 0 1 4 0 0 0 0 0 17 1.34 1.49
66 E -2 -1 -3 1 -6 0 7 -5 -3 -6 -6 -2 -5 -6 -4 1 -4 -6 -5 -5 3 2 0 5 0 3 79 0 0 0 0 0 0 0 0 8 0 0 0 0 1.62 1.53
67 S -2 -1 2 -3 -4 -3 -3 -4 -4 -3 -2 -2 -4 -5 -2 6 4 -6 -5 -4 0 3 8 0 0 0 0 0 0 1 5 1 0 0 2 58 22 0 0 0 1.06 1.56
68 R -4 8 -2 -4 -6 -2 -2 -5 -3 -2 -3 1 -1 -4 -5 -1 -4 -5 -4 -5 0 82 1 0 0 0 1 0 0 3 2 5 1 1 0 3 0 0 0 0 1.79 1.56
69 P -3 -2 -4 -2 -2 -2 -3 -3 -4 -4 0 2 -4 -5 7 -1 -2 -5 -5 -3 1 2 0 2 1 2 1 2 0 0 9 13 0 0 58 5 1 0 0 1 1.37 1.50
70 S 1 -1 0 -2 -1 -2 -2 -3 -4 -3 0 -3 -2 0 -2 5 -1 -5 -4 -2 12 3 5 1 1 1 1 1 0 1 9 0 1 4 1 52 3 0 0 3 0.69 1.50
71 R -1 4 2 -3 -5 2 0 -3 0 -5 -2 4 -4 -5 1 -2 -2 -5 -4 -3 4 27 10 1 0 8 6 2 2 0 5 24 0 0 7 2 2 0 0 1 0.64 1.49
72 L 0 4 0 -1 -3 0 -1 -2 -1 -2 -1 3 0 -1 -3 0 0 2 -1 -2 7 21 4 3 0 3 4 2 1 2 7 17 3 2 1 7 6 3 3 3 0.28 1.52
73 K -1 2 1 -1 -2 -1 1 2 0 -1 -2 2 0 0 -1 0 0 -5 -4 -2 5 9 6 3 1 2 11 16 2 3 4 13 3 4 3 8 5 0 0 2 0.19 1.50
74 K 0 0 2 1 0 -2 -3 1 -2 -3 -1 3 -2 -4 2 1 0 -5 -4 -3 8 6 11 8 2 1 1 10 1 1 7 16 1 1 10 9 7 0 0 1 0.27 1.50
75 D -2 -2 1 2 -5 -2 0 2 -2 -3 -3 1 -3 -2 -1 0 -2 8 0 0 2 2 8 10 0 1 6 14 1 1 2 8 1 1 3 7 2 20 4 8 0.59 1.50
76 E -1 -1 1 2 -3 3 4 -1 0 -5 -4 0 -2 -5 -3 1 0 -5 -3 -2 5 2 5 10 1 13 28 4 2 0 1 6 1 0 1 11 7 0 1 3 0.49 1.48
77 Y -1 -4 -3 -2 -5 0 -4 -5 3 -2 1 -4 1 3 -2 -1 -4 -2 7 -1 5 0 1 3 0 5 0 0 7 1 11 0 3 9 3 4 0 0 43 4 0.96 1.53
78 E -2 -1 1 3 1 -1 4 -4 -2 0 0 -2 -1 -2 -4 -2 -2 -5 -1 1 3 3 6 19 3 2 27 1 1 7 8 1 1 2 0 2 2 0 2 9 0.43 1.53
79 F -2 -2 -5 -5 1 -4 -5 -5 -4 2 -1 -4 1 7 -5 -4 -1 -3 2 2 3 3 0 0 3 0 0 0 0 11 4 0 3 45 0 0 4 0 5 16 0.97 1.33
80 F -4 -4 -5 -5 -4 -4 -5 -5 1 0 2 -4 3 6 -5 -2 0 3 4 -1 0 0 0 0 0 0 0 0 3 5 17 0 7 35 0 2 6 3 14 4 0.90 1.33
81 T -2 -2 -1 -5 -4 -4 -4 -5 -5 4 1 -4 1 0 -5 -4 0 -5 -3 5 3 2 4 0 0 0 0 0 0 23 11 0 3 3 0 0 5 0 0 43 0.79 1.33
82 H -2 1 0 5 -5 0 1 -1 0 -2 -5 1 -4 -1 -4 0 0 -5 -1 -2 2 8 4 36 0 3 10 4 2 2 1 10 0 3 0 5 5 0 2 2 0.57 1.33
83 L -2 -5 -5 -5 7 -4 -5 -5 -4 2 2 -5 1 3 -5 -2 -3 -4 -1 2 2 0 0 0 27 0 0 0 0 11 21 0 4 14 0 2 0 0 2 13 0.92 1.32
84 D -1 -1 -1 4 -5 0 5 -4 -2 0 -3 -1 -2 -3 -1 0 0 -5 -3 -3 4 3 2 21 0 2 37 0 1 5 2 2 1 1 3 6 6 0 1 2 0.61 1.33
85 K 0 -2 -1 -3 3 -2 -2 4 -4 -1 -2 1 2 1 1 -2 -2 -4 -4 1 7 1 3 1 7 2 2 29 0 3 2 8 5 7 7 2 2 0 0 10 0.37 1.31
86 R -2 1 2 1 -4 -1 2 -2 7 -2 -3 0 -4 -4 0 -1 1 -5 -3 -2 3 8 10 7 0 2 12 3 25 2 3 6 0 0 5 3 7 0 0 3 0.54 1.29
87 S -1 2 0 0 -1 0 3 1 1 -4 -4 1 -3 -5 -2 3 -1 -5 -4 -3 3 11 4 6 1 3 17 9 3 1 2 7 1 0 2 25 4 0 0 2 0.38 1.46
88 L -1 0 1 4 0 0 0 -2 -2 -1 0 1 -1 0 -4 0 0 -4 0 -1 4 6 5 21 2 3 6 2 1 4 11 8 2 4 1 7 5 0 3 5 0.18 1.36
89 P -1 -1 1 2 -4 2 3 0 0 -1 -4 0 -1 -4 2 0 -3 2 -1 -2 5 4 6 12 0 8 21 8 2 4 1 4 2 0 10 6 1 3 2 2 0.32 1.38
90 A 0 1 3 1 -4 1 2 -4 -1 -1 -2 2 -1 -3 0 -1 -1 -5 -4 0 8 7 15 7 0 6 12 1 1 5 4 14 1 1 4 3 4 0 0 6 0.26 1.43
91 L -3 -4 -2 -3 -2 -3 -5 -4 -5 2 4 -3 1 0 -5 -1 -2 -4 -1 3 2 1 2 2 1 1 0 1 0 11 40 1 3 4 0 6 2 0 2 21 0.62 1.59
92 T 0 0 2 1 -5 1 1 -1 1 1 0 2 1 -4 -2 0 -2 -5 -3 0 9 5 8 6 0 5 7 4 3 7 10 11 3 1 2 7 2 0 1 6 0.12 1.59
93 N 1 1 2 2 -2 3 2 -2 0 -4 -2 1 -3 -5 -3 0 -1 -5 -4 -4 11 6 9 10 1 16 15 2 2 1 4 10 1 0 1 7 4 0 0 1 0.38 1.59
94 I 3 -4 -3 -5 -2 -4 -2 -3 -2 2 2 -1 0 -2 -5 -1 -1 -5 -2 2 28 0 1 0 1 0 3 2 1 12 21 3 2 1 0 5 3 0 2 15 0.44 1.62
95 I -2 -4 -3 -5 0 -1 -2 -5 -5 4 3 -2 1 0 -5 -3 -1 -5 -2 1 4 1 2 0 2 2 3 1 0 26 33 3 3 3 0 1 4 0 1 10 0.60 1.62
96 K -1 1 -1 1 -1 1 3 -2 -1 -3 -1 3 -3 -3 -2 0 -1 -5 -3 -4 6 8 3 7 1 7 20 3 1 1 8 20 0 1 2 6 3 0 1 1 0.35 1.62
97 I 0 0 0 1 0 -1 2 -2 -1 -1 1 -1 2 -1 -4 2 -2 -5 -1 -2 9 6 5 7 2 2 15 3 1 3 15 4 4 2 0 15 2 0 2 2 0.19 1.59
98 L -2 -2 -3 -2 -4 -1 -3 -6 -2 1 5 -2 2 1 -5 -4 -2 -5 -4 1 3 3 1 2 0 3 1 0 1 6 56 3 4 5 0 0 2 0 0 9 0.76 1.62
99 R -1 4 -1 -1 -2 2 0 -1 -4 1 -1 3 0 -5 -4 0 -1 -5 -4 -1 4 20 2 3 1 10 5 5 0 7 5 21 2 0 0 6 4 0 0 5 0.39 1.60
100 H -1 2 2 1 -5 3 3 -1 2 -4 -4 1 -4 -5 -2 0 0 -5 -3 -4 4 12 8 7 0 12 21 4 5 1 1 7 0 0 1 7 6 0 1 1 0.44 1.58
101 D -3 2 1 2 0 2 2 -2 4 0 -2 1 -3 -3 -3 1 -1 -4 0 -3 1 11 7 10 2 8 12 3 9 6 4 8 0 1 1 9 4 0 4 1 0.28 1.53
102 I 1 -4 -2 -2 4 -3 -2 -3 1 1 0 -4 -3 0 -2 0 1 -2 -1 3 14 1 2 2 10 1 2 2 3 8 8 1 0 4 2 6 9 1 2 24 0.35 1.52
103 G 2 0 -1 0 1 1 -2 1 0 0 -2 0 -1 -4 -1 3 1 -4 -4 -2 15 6 3 4 3 6 1 10 2 5 5 6 1 0 3 20 7 0 0 3 0.20 1.52
104 A 1 -2 -1 -1 -4 -1 0 -2 -4 -2 -1 -2 2 4 -1 3 -1 -2 0 -1 11 2 2 4 0 2 5 3 0 2 6 2 5 20 4 21 4 1 3 4 0.31 1.56
105 T -2 -1 0 -2 -4 -2 -3 -1 0 0 0 -1 0 2 -1 0 2 -3 4 2 3 3 5 2 0 1 1 5 2 5 8 4 2 7 4 6 13 0 13 16 0.23 1.56
106 V -2 0 0 -1 2 -1 -2 -3 -4 0 0 3 -1 2 1 -2 -1 -2 -3 2 2 5 4 3 5 3 3 2 0 6 10 18 1 9 6 2 3 1 0 17 0.26 1.61
107 H -2 0 3 -1 -1 -1 -1 -3 3 0 -1 2 -1 -2 -2 0 -1 -5 -1 3 4 5 12 3 1 3 4 2 8 5 5 12 1 2 2 6 3 0 2 21 0.26 1.60
108 E -1 -4 -2 -1 -4 -2 2 -4 -3 3 3 -2 -2 0 -5 -2 -1 -5 -3 1 6 0 2 4 0 1 14 1 1 15 32 2 0 3 0 3 4 0 1 9 0.42 1.66
109 L -2 -3 -1 0 -4 -1 -2 3 -4 1 2 -1 -1 -1 -1 -1 0 3 -4 -1 3 1 3 5 0 3 2 21 0 7 23 5 1 3 3 3 7 4 0 5 0.27 1.67
110 S -1 -1 1 0 -5 0 -1 0 -4 0 -2 1 1 -5 1 2 1 -5 0 1 5 4 7 5 0 5 4 9 0 6 4 8 3 0 7 13 8 0 3 10 0.13 1.86
111 R -2 1 1 0 -5 1 1 -1 1 -1 -2 1 1 0 -1 0 0 3 2 -1 3 6 7 6 0 6 9 4 3 4 4 10 3 4 3 8 5 4 6 4 0.14 1.83
112 D -1 -4 3 2 -5 0 3 -2 1 -2 -2 0 -4 -1 1 0 0 -5 2 -2 5 0 12 11 0 3 17 3 3 3 4 5 0 2 8 7 7 0 6 3 0.27 1.78
113 K -1 0 1 0 3 1 0 -1 2 0 -1 0 2 1 0 0 0 -5 1 -4 6 6 5 6 5 5 6 6 5 6 6 6 5 5 6 6 6 0 5 0 0.11 1.89
114 K 0 0 0 2 1 0 0 1 -4 0 -2 3 1 -5 0 1 0 -5 -5 0 6 4 4 10 3 4 6 11 0 5 4 15 3 0 4 10 4 0 0 6 0.18 1.80
115 K 0 -4 1 0 -5 1 0 0 3 0 -1 0 2 1 -4 0 0 -4 2 0 6 0 6 6 0 6 6 6 6 6 6 6 6 6 0 6 6 0 6 6 0.13 1.67
116 D -1 0 1 0 3 1 0 -1 2 0 -4 0 -4 1 0 0 0 4 -4 0 6 6 6 6 6 6 6 6 6 6 1 6 0 6 6 6 6 6 0 6 0.17 1.78
117 T 0 0 1 0 3 1 0 0 -4 0 -1 0 2 -4 -4 0 0 -5 1 0 6 6 6 6 6 6 6 6 0 6 6 6 6 0 0 6 6 0 6 6 0.13 1.67
118 V 0 -4 0 0 -4 0 -1 -1 2 1 -1 -1 2 0 -4 -1 0 -5 -4 4 6 0 4 6 0 4 4 6 5 9 4 4 5 4 0 6 5 0 0 27 0.28 1.63
119 P 1 -1 -2 -2 -3 -1 2 -1 1 0 -2 -2 -3 -3 6 -1 -1 -4 -3 -1 11 3 1 1 0 2 15 4 4 7 3 1 0 1 39 3 3 0 0 3 0.69 0.70
120 W -3 -3 -3 -1 -3 -3 -3 -3 -3 0 -3 -3 -2 -1 -3 0 2 11 0 -3 1 1 1 4 0 1 1 1 0 8 1 1 0 1 1 10 14 54 0 1 1.66 0.71
121 F 1 1 -3 -3 -3 -3 -3 -3 -2 -1 -2 -3 -2 6 -3 0 0 -1 3 -2 14 8 1 1 0 1 1 1 0 3 1 1 0 48 1 6 6 0 7 1 0.73 0.71
122 P -2 -2 -3 -3 -4 -2 -2 -3 -3 -4 -4 2 -3 -4 8 -2 -2 -4 -4 -3 1 1 1 1 0 1 1 1 0 1 1 14 0 1 75 1 1 0 0 1 1.81 0.71
123 R -3 1 1 -3 4 2 1 0 3 -4 0 1 3 -5 1 -3 1 -5 -4 -4 0 8 8 0 8 8 8 8 8 0 8 8 8 0 8 0 8 0 0 0 0.37 1.22
124 T -3 2 0 2 -1 0 0 -4 5 -5 -4 4 1 -5 -4 2 -1 -5 -2 -3 0 10 4 10 2 2 4 0 14 0 0 29 5 0 0 15 4 0 1 1 0.58 1.04
125 I 0 -2 -4 1 -4 -4 -1 -5 -5 6 0 -4 -2 -3 0 -2 -3 -5 -4 2 9 3 0 9 0 0 3 0 0 51 5 0 0 0 4 3 0 0 0 12 0.72 1.04
126 Q 1 2 1 -3 -2 0 1 -1 1 -4 -4 0 -4 2 -4 3 -1 -4 0 -4 10 10 8 0 1 5 8 5 3 0 0 6 0 12 0 29 3 0 2 0 0.39 1.04
127 E -4 0 -1 6 -6 1 4 0 4 -6 -6 -2 -5 -5 -4 -2 -3 -6 -4 -5 0 5 0 49 0 5 25 6 10 0 0 0 0 0 0 0 0 0 0 0 1.13 0.98
128 L -1 -4 -5 -5 -3 -4 -5 -5 -5 0 5 -4 -1 1 -5 -1 1 2 -3 0 4 0 0 0 0 0 0 0 0 4 68 0 0 4 0 5 8 3 0 5 0.87 0.98
129 D -3 -3 0 7 -5 3 1 -4 -3 -5 -6 1 -5 -6 -4 0 -3 -6 -5 -5 0 0 3 64 0 14 4 0 0 0 0 7 0 0 0 8 0 0 0 0 1.29 0.98
130 R -3 3 0 -1 -4 1 0 -3 1 -2 -1 3 -3 -1 0 0 0 -4 2 0 0 14 3 2 0 7 4 1 4 1 7 24 0 2 5 6 5 0 7 8 0.29 0.96
131 F -3 -4 -4 -4 7 -4 -4 -4 -4 2 1 -4 -2 2 -4 1 0 -3 1 0 1 0 0 0 29 0 0 1 0 14 12 0 0 11 0 12 6 0 6 7 0.77 1.03
132 A 0 1 1 1 4 1 -3 0 3 -4 -4 -3 -3 -3 -4 0 1 -4 2 0 8 8 8 8 8 8 0 8 8 0 1 0 0 0 0 8 8 0 8 8 0.30 1.23
133 N -2 -1 4 1 -2 2 0 1 7 -6 -5 -1 -1 -5 1 -1 -3 -5 -3 -5 2 3 18 8 1 12 5 11 25 0 0 4 1 0 6 3 1 0 0 0 0.72 1.21
134 Q -3 2 -1 -1 2 2 2 -5 3 -3 2 -1 -2 -4 -4 -1 0 -5 -4 1 0 13 2 3 4 11 16 0 8 0 23 3 0 0 0 3 5 0 0 9 0.38 1.15
135 I 0 -4 -1 -5 0 -4 -4 -5 2 4 2 -2 2 -3 -5 -3 1 -5 -4 4 8 0 4 0 2 0 0 0 5 21 16 2 6 0 0 0 7 0 0 29 0.57 1.13
136 L -3 1 -4 -1 -4 -3 -2 -1 -4 0 3 -3 5 -3 -5 -1 3 -5 -4 -1 0 7 0 5 0 0 3 6 0 3 30 0 18 0 0 3 23 0 0 3 0.58 1.19
137 S 0 0 0 0 -5 0 1 -2 2 -1 -2 3 4 -5 -4 2 -1 -5 -4 -1 7 5 5 4 0 4 11 2 5 4 3 22 11 0 0 13 2 0 0 3 0.34 1.26
138 Y 0 1 0 -4 -4 -3 -4 -5 2 0 -1 -3 2 3 -5 0 0 -3 4 2 7 9 4 0 0 0 0 0 4 4 4 0 6 14 0 9 5 0 13 19 0.39 1.11
139 G -3 -3 2 2 -4 2 1 1 -3 1 -4 1 -3 -5 -4 1 1 -5 -4 1 0 0 10 10 0 10 10 10 0 10 0 10 0 0 0 10 10 0 0 10 0.30 1.00
140 A 2 -2 -2 -2 -4 -3 1 0 -4 -1 -4 -2 -4 -5 5 1 -1 -6 -5 -1 22 1 1 2 0 0 9 7 0 5 0 2 0 0 32 13 2 0 0 4 0.71 1.18
141 E 1 -3 1 4 -5 1 4 -3 4 -5 -5 -3 -4 -5 -4 -1 1 -6 -4 -3 14 0 5 21 0 5 28 2 11 0 0 0 0 0 0 3 10 0 0 2 0.70 1.17
142 L -1 -4 1 -4 -4 0 -4 -5 -4 -2 3 -2 0 0 4 -2 2 -5 -4 -3 4 0 7 0 0 4 0 0 0 0 36 1 2 4 19 3 13 0 0 0 0.49 1.17
143 D 0 2 1 4 2 2 -1 -4 -3 -5 -5 -2 -1 -5 -4 2 0 -5 -5 -4 6 11 7 29 4 9 3 0 0 0 0 0 2 0 0 14 7 0 0 0 0.50 1.22
144 A 1 -2 -3 1 1 0 2 -4 1 0 0 0 3 -4 0 0 0 -5 -4 -2 12 2 0 7 3 5 12 0 3 7 9 6 8 0 5 7 4 0 0 1 0.11 1.22
145 D 1 2 -1 3 -4 1 -1 -2 -3 1 0 -1 -3 0 -4 -1 -3 -4 -1 -3 12 13 3 19 0 8 3 2 0 9 8 4 0 4 0 3 0 0 2 0 0.19 1.11
146 H -3 2 -3 2 -4 0 -2 -4 5 -4 -1 -2 -3 2 3 1 -3 -3 3 -4 0 11 0 11 0 5 0 0 13 0 5 0 0 8 14 12 0 0 11 0 0.39 0.94
147 P 1 -3 -3 -3 -4 2 1 1 -3 -2 0 -3 -2 -4 2 -2 1 -4 -4 1 11 0 0 0 0 11 11 11 0 0 11 0 0 0 11 0 11 0 0 11 0.19 0.89
148 G 1 -3 -2 0 0 -1 1 6 -3 -5 -4 -1 -4 -5 -3 -2 0 -4 -4 -4 9 0 0 5 2 3 9 56 0 0 1 4 0 0 0 1 6 0 0 1 0.88 1.01
149 F 0 -1 -4 -4 -4 -3 -2 -4 0 -1 -1 -1 5 6 -4 -3 -3 -2 3 -1 7 3 0 0 0 0 3 1 2 2 4 4 19 41 0 1 0 0 8 4 0.86 1.04
150 K 1 -1 0 -2 -4 -1 -2 0 3 -4 -3 3 -3 -4 3 2 2 -4 -3 -3 11 2 3 2 0 3 0 6 7 0 2 17 0 0 15 14 16 0 0 0 0.42 1.04
151 D 0 -4 0 6 -4 -3 0 1 -3 -4 -3 -3 -4 -5 0 -2 1 -5 -4 -4 6 0 3 57 0 0 3 11 0 0 2 0 0 0 4 0 11 0 0 0 1.00 1.04
152 P 0 -1 0 1 -4 1 1 -1 -2 0 -1 1 -1 -4 2 -1 2 -5 -4 1 7 2 5 7 0 7 9 4 1 4 5 8 1 0 12 2 13 0 0 13 0.20 1.04
153 V 1 -4 -1 -2 -4 -2 2 -4 -4 0 -1 -2 0 -2 -4 0 0 -5 -4 4 15 0 3 2 0 1 13 0 0 4 4 1 2 1 0 7 6 0 0 41 0.48 1.05
154 Y -3 -3 -3 -4 -4 2 -3 -4 -2 -4 -3 -3 -3 3 -4 1 3 -1 7 -3 0 0 0 0 0 13 0 0 0 0 0 0 0 10 0 11 22 0 44 0 1.07 1.02
155 R 1 5 -2 -1 -5 0 -3 -2 -3 -1 -4 0 -1 -5 2 -3 1 4 -4 -2 14 37 2 3 0 3 0 3 0 4 0 5 2 0 9 0 11 6 0 2 0.63 1.18
156 A 1 0 -2 -1 3 2 2 -4 -3 -3 -3 5 0 -5 2 -1 -2 -5 -4 -2 11 4 1 2 6 7 13 0 0 1 2 36 2 0 8 2 2 0 0 2 0.56 1.18
157 R -3 6 2 -3 -5 1 -2 -4 -3 -4 1 2 -3 -5 2 -1 -3 -5 -4 -4 0 45 11 0 0 5 0 0 0 0 14 9 0 0 11 5 0 0 0 0 0.82 1.00
158 R -3 6 -3 0 -4 1 -2 -4 -3 -3 -1 1 2 -4 -4 -3 0 -4 -3 0 1 50 0 6 0 6 1 1 0 0 7 7 6 0 0 1 6 0 0 7 0.80 1.06
159 K 0 1 1 1 -4 1 1 0 -3 -4 -4 1 3 -4 -4 0 1 -4 2 0 8 8 7 8 0 7 8 8 0 0 1 8 7 0 0 8 8 0 7 8 0.22 1.34
160 Q -2 0 -3 2 -5 3 2 -4 2 0 -2 -1 1 0 -4 0 -2 1 3 -1 4 4 0 14 0 13 14 1 5 6 2 3 4 4 0 8 1 2 12 3 0.36 1.46
161 F -4 -5 0 -5 -4 -4 -5 -2 0 4 0 -4 -2 5 1 -4 -4 3 4 -1 0 0 6 0 0 0 0 3 3 29 8 0 0 21 8 0 0 3 13 3 0.75 1.45
162 A 4 -4 -1 0 0 1 -2 -2 -4 -4 -2 -3 -1 -1 -2 2 1 -5 -4 0 42 0 3 5 2 6 2 3 0 0 3 0 1 3 2 14 7 0 0 6 0.54 1.56
163 D 0 2 0 3 -5 2 2 -2 5 -5 -3 0 0 -5 0 -1 -1 -5 -4 -3 6 10 3 18 0 9 15 3 13 0 3 5 2 0 4 3 4 0 0 2 0.45 1.60
164 I 0 -1 -4 -2 1 0 -4 -5 -5 3 2 -1 1 -1 -1 -1 3 -5 -4 1 8 4 0 3 3 4 0 0 0 14 20 4 3 3 3 4 18 0 0 9 0.33 1.61
165 A 4 1 0 0 -4 0 -1 0 1 -5 -2 0 -4 -5 1 0 0 -5 -4 -4 36 8 5 5 0 5 4 6 4 0 4 4 0 0 7 7 5 0 0 0 0.43 1.64
166 Y -1 0 1 0 -5 1 0 -1 2 0 -1 0 2 1 0 0 0 -5 1 0 6 6 5 6 0 5 6 6 5 6 6 6 5 5 6 6 6 0 5 6 0.08 1.89
167 N -1 0 2 2 -5 1 -1 -1 3 -2 0 1 -4 2 -1 -1 -1 -5 -1 0 5 6 9 13 0 5 3 4 7 2 11 9 0 8 3 4 4 0 2 6 0.18 1.75
168 Y 1 -2 -4 -5 0 -1 -4 -5 4 -4 -2 -1 -4 1 0 -1 -4 4 6 1 12 2 0 0 2 3 0 0 10 0 3 4 0 6 6 4 0 6 30 10 0.76 1.75
169 R -2 4 0 -1 -5 0 -3 -2 2 -1 -2 3 1 -5 -1 -1 2 -5 0 -1 4 19 3 4 0 4 0 4 6 4 5 17 3 0 4 4 12 0 3 4 0.34 1.89
170 H -1 0 0 0 2 0 0 -1 2 0 -1 0 2 1 0 -1 0 4 1 -1 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 0.09 2.12
171 G 0 -3 1 1 -4 1 0 0 3 0 -4 0 2 -4 1 0 0 4 -4 0 7 0 7 7 0 7 7 7 6 7 1 7 6 0 7 7 7 6 0 7 0.23 1.56
172 Q -3 -1 1 5 0 4 1 -2 -1 -2 -3 0 -1 -5 -4 0 -1 -5 -5 0 2 3 5 28 2 21 7 2 1 2 2 5 1 0 0 7 3 0 0 7 0.58 1.60
173 P 0 -1 -2 1 -5 1 1 -2 0 -2 -3 0 -4 -5 6 0 -1 -5 -5 -3 9 3 2 6 0 7 10 3 3 2 2 5 0 0 39 5 3 0 0 2 0.77 1.58
174 I -3 -1 0 0 -4 4 -1 -2 1 4 0 -1 1 -4 0 -2 -1 -5 -4 0 1 3 4 5 0 21 4 3 3 22 9 3 4 0 4 3 3 0 0 7 0.39 1.56
175 P -1 -2 0 0 -5 -1 -1 4 2 -5 -5 -1 -4 -1 5 -3 -2 -5 -4 -2 5 3 4 4 0 3 4 28 4 0 1 3 0 3 29 0 3 0 0 3 0.70 1.60
176 R -4 0 1 0 3 1 0 -5 2 0 -1 0 2 1 -5 0 0 4 2 0 0 6 6 6 6 6 6 0 6 6 6 6 6 6 0 6 6 6 6 6 0.23 1.78
177 V -1 -2 -2 0 -3 -2 0 -4 -1 4 -1 -3 -1 -3 -2 -2 -1 -4 -1 4 5 2 2 6 0 2 7 1 1 27 3 1 1 0 2 2 3 0 2 31 0.54 1.30
178 E 0 -1 0 2 -4 0 4 -2 2 -2 -2 -1 -3 -4 -1 -1 0 -4 -3 -2 7 3 4 13 0 4 34 3 6 2 4 3 0 1 3 3 7 0 0 3 0.45 1.12
179 Y -4 -3 -4 -4 -4 -3 -4 -4 3 -3 -3 -4 -3 3 -4 -3 -3 8 8 -3 1 1 1 1 0 0 1 1 7 1 1 1 0 9 1 1 1 18 56 1 1.70 1.05
180 M -1 -4 0 0 2 -3 -3 0 -4 -4 -2 -1 1 0 1 3 4 -5 -4 -3 5 0 4 5 4 0 0 8 0 0 5 4 4 4 6 21 29 0 0 0 0.47 1.45
181 E 0 -1 0 2 -5 1 3 -1 1 -1 -2 0 -4 -4 2 -1 -1 -5 0 -2 7 4 3 10 0 7 23 4 3 3 4 7 0 0 9 5 4 0 3 3 0.29 1.45
182 E 1 -1 -1 1 -1 2 5 -2 -1 -1 -4 -2 -3 -4 -2 0 0 -1 -4 0 11 3 2 7 1 10 35 2 1 5 1 1 0 0 2 6 6 1 0 6 0.46 1.17
183 E -3 -2 1 3 -5 1 6 -3 -2 -4 -4 -2 -4 -4 -3 -2 -3 -4 -4 -4 1 1 8 18 0 4 61 1 0 1 1 1 0 0 1 1 1 0 0 1 1.15 1.04
184 K -3 -1 2 0 -4 2 -1 -3 7 1 -2 0 -3 -1 -3 -2 0 -4 -2 -1 1 2 10 4 0 8 3 1 35 9 3 6 0 2 1 1 7 0 0 5 0.71 1.04
185 K 3 0 0 2 -1 0 2 -1 -1 -3 -3 1 -1 -4 -3 -1 -1 4 -3 -2 25 4 5 10 1 4 15 3 2 2 2 10 2 0 1 3 2 5 0 2 0.34 1.18
186 T -1 -1 -3 -4 -3 -3 -3 -4 -4 3 1 -3 1 -3 -4 -2 5 -4 -3 2 4 4 0 1 0 0 1 1 0 17 10 1 4 0 1 1 39 0 0 17 0.68 1.18
187 W -4 0 -5 -5 -4 -4 -4 -4 -4 -4 -3 -4 -3 1 -5 -4 -4 12 2 -4 1 5 0 1 0 0 1 1 0 1 1 1 0 5 1 1 1 76 6 1 2.92 1.18
188 G -1 3 0 1 -5 1 -1 2 3 -1 -4 1 1 -4 -4 0 -1 -5 0 -4 5 18 4 7 0 7 4 19 6 4 1 8 4 0 0 6 4 0 4 0 0.37 1.62
189 T 0 3 -1 1 2 1 1 -4 1 0 -1 -1 1 0 -4 -1 2 -5 0 0 6 14 3 7 4 5 8 0 4 6 6 4 3 3 0 3 14 0 4 6 0.19 1.62
190 V -1 -5 -5 -5 2 -4 -5 -5 -5 2 3 -5 -2 -3 -2 -4 -3 -5 -4 5 4 0 0 0 5 0 0 0 0 8 29 0 0 0 2 0 0 0 0 47 0.91 1.36
191 F -2 -4 -5 -5 0 -4 -5 -5 1 0 0 -5 4 5 -5 -2 -2 4 6 0 2 0 0 0 2 0 0 0 4 4 7 0 11 24 0 3 3 5 27 6 0.94 1.48
192 K 0 4 1 1 -5 0 2 -1 0 -3 -3 0 -4 -5 -1 0 1 -5 -4 -2 8 25 7 7 0 4 12 5 2 1 3 5 0 0 3 6 10 0 0 3 0.37 1.48
193 T -2 5 0 -2 -1 2 2 -4 -1 -2 -2 2 -1 -5 -4 0 1 -5 -4 -3 2 28 5 2 1 7 14 0 2 3 5 13 1 0 0 6 9 0 0 2 0.52 1.48
194 L -4 1 1 -4 -5 5 -3 -5 1 0 3 -3 2 -4 -5 -1 -1 -5 -4 -1 0 8 8 0 0 26 0 0 4 4 33 0 4 0 0 3 3 0 0 5 0.68 1.56
195 K 0 0 -1 -4 0 1 -1 -3 3 -1 0 2 3 -1 -5 0 1 1 -1 1 7 5 3 0 2 5 3 2 7 2 11 14 6 2 0 6 8 2 2 12 0.20 1.56
196 S -1 0 1 0 3 1 0 -1 2 0 -1 0 2 -5 1 0 0 -6 -5 0 6 6 6 6 6 6 6 6 6 6 6 6 6 0 6 6 6 0 0 6 0.14 1.78
197 L -1 -1 0 -6 1 -1 -5 -3 0 0 4 0 2 0 -6 -4 -2 -5 1 1 4 3 4 0 3 3 0 2 2 4 45 6 5 3 0 0 2 0 4 9 0.54 1.61
198 Y -1 -5 -2 -6 -5 -4 -5 -3 3 1 3 -3 1 0 -6 -2 -2 3 5 0 5 0 2 0 0 0 0 2 8 9 31 2 4 2 0 3 2 3 22 6 0.67 1.61
199 K 0 2 0 -1 -5 1 1 -2 1 -3 -3 1 1 -6 4 0 -1 -6 -5 -2 6 10 5 2 0 7 9 2 4 2 2 9 3 0 24 7 4 0 0 3 0.45 1.61
200 T -1 0 -1 2 -5 0 -1 3 -1 -4 -3 2 -4 -5 -1 0 3 -6 -3 -3 4 5 2 12 0 4 2 20 2 1 3 16 0 0 2 5 20 0 1 1 0.42 1.51
201 H -3 4 -1 -2 -1 -3 -4 -5 7 -2 0 0 -1 -1 -5 -3 -1 -4 3 1 1 20 2 2 2 0 0 0 28 1 9 4 2 3 0 1 3 0 11 11 0.78 1.51
202 A 6 -5 -5 -5 2 -4 -4 -3 -5 -4 -1 -4 0 -2 -4 -1 -1 -5 -4 -1 77 0 0 0 4 0 0 0 0 0 5 0 2 2 0 3 4 0 0 3 1.25 1.51
203 C 0 -5 -2 -5 10 -5 -5 -5 4 -2 -4 -5 -4 0 -1 0 -1 -5 -2 -1 9 0 1 0 55 0 0 0 10 2 0 0 0 4 3 7 3 0 1 4 1.65 1.48
204 Y -1 0 1 0 -5 1 0 -1 2 0 -1 0 2 -4 0 0 0 -5 1 0 6 6 6 6 0 6 6 6 6 6 6 6 6 0 6 6 6 0 6 6 0.10 1.78
205 E 0 0 -3 0 1 1 5 -2 1 -4 -2 -1 -4 0 0 0 -3 -5 -4 -1 8 4 0 4 4 6 36 4 4 0 4 4 0 4 4 7 0 0 0 5 0.48 1.62
206 Y -3 -4 -4 -5 -5 -1 -4 -5 4 -2 -2 -4 -3 5 -5 -4 -4 -1 7 -2 2 0 0 0 0 2 0 0 11 2 3 0 0 27 0 0 0 0 47 3 1.46 1.32
207 N -3 -1 3 -1 0 0 -4 -5 -2 2 4 -2 3 -1 -5 -2 -3 -5 -4 0 1 4 14 3 2 4 0 0 1 10 40 3 6 2 0 3 0 0 0 6 0.53 1.36
208 H 0 2 1 3 0 2 3 -3 3 -4 -5 0 -1 -3 -2 -2 -2 -5 1 -3 7 10 5 15 2 10 22 1 7 1 0 5 2 1 1 2 2 0 5 1 0.46 1.46
209 I 2 -5 2 -1 2 -4 -4 5 0 -1 -3 -4 0 -3 -5 -1 -2 -5 -2 0 18 0 12 3 4 0 0 38 2 3 2 0 2 1 0 4 1 0 2 7 0.64 1.46
210 F -2 -5 -5 -6 -4 -5 -5 -6 -5 1 4 -2 1 5 -3 -5 -2 4 0 0 2 0 0 0 0 0 0 0 0 8 39 3 3 28 2 0 2 5 2 6 0.89 1.42
211 P 0 0 -1 1 -2 1 2 -1 1 -3 -3 1 0 -5 4 -1 -2 -5 -4 -3 8 4 3 7 1 6 14 6 3 1 3 10 3 0 21 4 2 0 0 2 0.37 1.36
212 L -2 1 -3 0 -4 1 -1 -2 0 0 4 3 0 -3 -4 -2 -2 -4 -4 -2 3 9 0 6 0 6 3 3 2 5 36 16 2 0 0 2 3 0 0 2 0.40 1.34
213 L -1 -4 -4 -4 -3 -4 -4 -1 -4 1 5 -4 2 2 -4 -4 -3 -3 -3 -1 5 1 1 1 0 1 1 5 0 7 58 1 4 9 1 1 1 0 0 3 0.81 1.27
214 E -1 -1 -1 1 -1 3 3 -1 -2 0 -1 0 -1 -3 -1 1 -1 -3 -3 0 4 3 2 8 1 12 23 4 1 5 6 6 2 1 3 9 4 0 1 6 0.25 1.14
215 K -1 1 -1 2 -3 0 2 -1 -1 -1 -1 3 -1 -2 -2 -1 -1 -3 -2 -2 4 8 3 13 1 4 16 5 1 3 6 18 1 2 2 3 3 0 1 4 0.26 1.02
216 Y 1 -1 2 0 -1 -1 2 -2 3 -2 -1 -1 -2 0 -2 -1 0 -2 3 -2 13 3 10 4 2 2 12 3 8 2 6 4 1 4 2 5 6 0 9 3 0.20 1.02
217 C -1 0 -1 -1 7 -1 -2 0 -3 -1 1 -1 0 -2 -2 0 0 -3 -3 -1 5 5 2 3 26 2 2 7 1 4 17 4 2 1 2 6 6 0 1 3 0.51 1.10
218 G 0 0 1 -1 -4 -3 -3 5 0 1 -2 -2 -3 -4 -3 -2 -3 -4 -4 -1 7 5 6 3 0 1 2 49 2 8 4 2 0 1 2 2 1 0 0 5 0.71 1.34
219 F -2 -2 -5 -5 -1 -4 -5 -4 -3 1 3 -4 3 4 -5 -3 -4 -2 6 -1 3 3 0 0 1 0 0 1 0 9 27 0 6 16 0 1 0 0 27 2 0.85 1.46
220 H 0 3 0 -1 0 -1 0 0 -1 -4 -2 -1 -4 -3 3 2 0 -5 -4 -1 6 17 5 3 2 2 5 8 1 0 4 3 0 1 14 19 5 0 0 4 0.32 1.46
221 E 1 2 -2 0 -3 0 4 -1 -1 0 -2 1 -4 -5 3 -1 -1 -5 -5 -2 11 9 1 5 1 3 25 5 2 5 4 7 0 0 12 3 3 0 0 2 0.36 1.52
222 D -3 -2 1 5 -4 0 3 0 1 -4 -4 -1 -3 -1 0 0 1 -4 -1 -4 1 2 6 32 0 4 16 7 3 1 1 2 0 3 4 6 8 0 2 1 0.52 0.98
223 N -1 4 2 -1 -1 1 0 1 3 -3 -4 1 -1 -1 -3 0 -1 -4 -1 -3 4 23 9 4 1 6 6 12 6 2 1 7 1 2 1 7 3 0 2 2 0.32 0.99
224 I -1 -4 -4 -4 -3 -4 -4 -4 -4 6 1 -4 2 -2 -4 -3 -1 -4 -3 3 6 1 0 1 0 0 1 1 0 53 9 1 4 0 1 1 3 0 0 18 0.90 1.01
225 P -1 -4 -4 -3 -4 -3 -1 -4 -4 0 -4 -3 -4 -4 8 -3 -3 -5 -4 -3 4 1 0 1 0 0 5 1 0 5 1 1 0 0 78 1 1 0 0 1 1.97 1.01
226 Q -3 1 1 3 -1 6 0 -3 0 -4 -4 1 -3 -5 -3 0 -2 -4 -4 -2 1 6 7 19 2 41 3 1 2 0 1 7 0 0 0 6 2 0 0 3 0.78 1.05
227 L -3 -4 -4 -5 -4 -2 -4 -5 1 1 4 -2 2 5 -2 -4 -3 -3 0 0 1 0 0 0 0 2 0 1 5 8 39 2 6 25 3 1 0 0 2 4 0.72 1.05
228 E 0 1 -1 3 -4 3 3 -1 -1 -4 -3 -1 -1 -4 0 1 -2 -4 0 -2 7 8 3 15 0 12 23 4 1 0 2 3 1 0 4 8 2 0 3 3 0.38 1.19
229 D 0 0 -1 5 -5 1 3 -1 1 -3 -3 -1 -4 -3 -4 -2 0 -5 -4 -2 7 5 1 36 0 5 20 4 3 1 3 2 0 1 0 1 6 0 0 3 0.62 1.19
230 V -1 -4 -4 -4 -3 -4 -4 -4 -4 3 1 -4 3 -3 -4 -1 0 -4 -3 5 5 0 0 0 0 0 1 1 0 19 13 1 8 0 0 5 6 0 0 38 0.71 1.21
231 S -1 -3 4 0 1 -3 -3 -1 1 -2 -4 -3 -4 -4 -1 4 0 -4 0 -4 4 0 23 5 3 0 0 3 3 3 1 0 0 0 3 39 6 0 4 0 0.66 1.24
232 Q -1 0 1 0 3 1 0 -1 2 0 -1 0 2 -5 0 0 0 4 -4 0 6 6 5 6 5 5 6 6 5 6 6 6 5 0 6 6 6 5 0 6 0.14 1.89
233 F -2 0 -1 -5 1 -1 -1 -2 1 -1 -2 0 -4 6 0 -2 -1 2 2 1 4 5 4 0 3 3 3 3 3 4 3 5 0 29 6 3 4 3 6 9 0.45 1.89
234 L -4 -5 -5 -5 -4 -4 -5 -5 -5 1 6 -5 2 1 -1 -5 -4 -4 -3 0 1 0 0 0 0 0 0 0 0 5 72 0 4 5 4 0 0 0 0 4 1.20 1.53
235 Q 0 1 -1 -1 -5 2 0 -1 2 -3 -2 4 2 -2 -4 1 -1 -5 -1 -3 6 6 2 3 0 9 6 4 4 2 4 30 6 2 0 10 2 0 2 2 0.41 1.56
236 T 2 1 -2 1 0 0 3 -2 -3 -4 -2 2 -3 -5 1 0 0 -5 -4 -3 17 9 1 7 2 4 19 2 0 0 5 12 0 0 8 7 5 0 0 2 0.34 1.17
237 C 1 3 -2 -3 2 0 1 -4 1 0 0 1 0 -3 -4 0 1 -4 -3 -2 12 19 1 0 5 3 11 1 4 5 10 9 3 1 0 5 9 0 0 2 0.27 1.15
238 T -2 -3 -2 -3 -3 -2 -3 -1 -3 -3 -2 -3 -3 -4 -3 2 7 -4 -3 -2 2 1 1 1 0 1 1 4 0 1 2 1 0 0 1 12 71 0 0 2 1.18 1.11
239 G -2 -2 1 -1 -4 0 -3 6 -1 -5 -5 -3 -4 -5 -4 -1 -3 -4 -4 -5 1 2 5 3 0 4 0 75 2 0 1 0 0 0 0 4 0 0 0 0 1.35 1.03
240 F -4 -4 -5 -5 -4 -4 -4 -4 -4 -3 -2 -4 2 6 -5 -4 -4 10 1 -3 1 0 0 0 0 0 0 1 0 0 2 0 6 37 0 1 0 47 2 0 2.09 1.03
241 R 0 3 -1 -2 -2 3 1 -1 1 -3 -3 0 -1 -4 -3 1 3 -4 -3 -3 9 15 2 1 1 14 10 5 3 1 2 5 1 0 1 8 22 0 0 1 0.39 1.00
242 L 0 -4 -4 -4 1 -4 -4 -4 -4 3 4 -4 0 -1 -4 -2 0 -3 0 3 8 1 0 1 3 0 1 1 0 16 36 1 1 2 1 2 4 0 4 19 0.54 1.00
243 R 0 4 -3 -3 0 1 -1 -3 -3 -1 -2 0 -2 -3 -3 -1 -1 -4 0 3 8 29 0 1 2 6 4 2 0 2 3 4 0 0 1 3 3 0 4 28 0.47 1.00
244 P 2 -2 -2 -1 -2 -2 -2 -1 -3 -3 -4 -1 -2 -4 7 -1 -1 -2 -4 -2 18 2 1 4 1 1 1 4 0 1 1 4 1 0 50 2 3 1 0 3 1.05 1.00
245 V 2 -4 -4 -4 0 -3 -4 -2 -4 0 -1 -4 -2 -3 -4 -3 0 -4 -3 6 15 1 0 1 2 0 1 3 0 2 3 1 0 0 1 1 4 0 0 64 0.89 1.00
246 A 2 -2 -3 1 -4 1 0 0 1 -4 -4 -1 -3 -2 5 0 -1 -4 -3 -2 22 2 0 7 0 6 7 6 4 1 1 3 0 2 30 5 2 0 0 2 0.58 0.96
247 G 1 -4 0 0 -4 -3 -1 6 -3 -4 -4 -3 0 -4 -3 -2 -3 -4 -4 -4 11 1 3 5 0 0 3 67 0 1 1 1 3 0 1 1 1 0 0 1 1.15 0.96
248 L -2 -4 -4 -4 -3 -1 -4 -2 -3 0 4 -4 1 3 -4 -3 -3 1 3 -1 4 1 0 1 0 3 1 3 0 5 50 1 3 11 1 1 1 2 11 2 0.65 0.96
249 L -3 -4 -4 -4 2 -4 -4 -5 -4 4 4 -4 2 -2 -4 -4 -3 -4 -3 3 1 1 0 1 4 0 1 1 0 30 38 1 5 0 1 1 1 0 0 16 0.79 0.96
250 S -1 1 1 0 -4 -2 -2 -2 1 -3 -4 -1 -3 -4 6 3 0 -4 -4 -3 2 7 5 5 0 0 1 3 4 2 1 2 0 0 37 23 6 0 0 1 0.80 0.96
251 S 1 -3 0 2 -4 1 0 -1 -1 -3 -2 -3 -3 2 4 0 -3 -3 0 -2 12 1 4 14 0 7 5 5 1 1 3 1 0 11 23 6 1 0 3 2 0.43 0.96
252 R 0 5 0 2 -4 0 0 -2 3 -4 -2 0 -3 -2 -1 -1 0 -4 -3 -2 8 34 3 12 0 3 6 3 6 1 3 3 0 2 3 3 6 0 0 4 0.47 1.08
253 D 0 1 0 4 -4 0 2 -4 1 -1 -1 -1 -3 -4 0 -2 0 -4 -4 1 7 9 3 23 0 4 14 1 4 3 5 2 0 0 4 2 6 0 0 12 0.32 1.08
254 F -4 -4 -4 -4 -4 -4 -4 -4 -3 -2 -2 -4 -2 8 -4 -4 -4 2 3 -3 1 1 0 1 0 0 1 1 0 1 1 1 0 80 1 1 1 3 7 1 1.77 0.97
255 L -3 -4 -4 -4 0 -4 -4 -4 -3 0 3 -4 3 6 -4 -4 -2 -2 3 -2 1 1 0 1 2 0 1 1 0 3 27 1 8 42 1 1 3 0 8 1 0.94 0.97
256 G 2 -1 1 2 -4 0 4 0 -3 -4 -4 -1 -3 0 -3 1 -1 2 -2 -3 18 2 6 11 0 3 27 8 0 1 1 3 0 4 1 8 3 3 1 1 0.40 0.97
257 G -1 -3 -3 -3 0 -2 -1 2 5 -2 2 -3 2 2 -4 1 -3 -3 0 -2 4 1 0 1 2 1 4 14 16 1 24 1 6 8 1 10 1 0 3 1 0.38 0.97
258 L -3 -3 -4 -4 -3 2 -3 -4 -4 1 5 -3 1 -1 -4 -4 -3 -1 -3 -1 1 1 0 1 0 12 1 1 0 5 71 1 2 1 1 1 1 1 0 1 0.94 0.97
259 A 6 -1 -2 -3 -3 -1 -2 0 -3 -3 -2 -2 -3 -4 -3 1 -2 -4 -1 -2 68 3 1 1 0 2 2 5 0 1 3 1 0 0 1 10 1 0 2 1 0.87 0.97
260 F -2 -1 4 1 -4 1 0 -2 2 -3 -2 -1 -1 4 -4 -1 -2 -3 2 -3 3 3 25 9 0 6 6 3 6 1 3 2 1 19 1 2 1 0 8 1 0.49 0.97
261 R -2 6 0 -3 -1 0 -2 0 0 -4 -4 3 -3 -4 -2 -1 -3 -4 -3 -4 2 47 5 1 2 3 1 8 2 1 1 22 0 0 2 3 1 0 0 1 0.87 0.94
262 V -2 3 -2 -3 -3 1 -1 -3 -1 0 0 1 -1 -2 -3 -2 -1 -4 -1 4 2 19 2 1 0 6 4 2 1 3 8 7 1 1 1 2 4 0 3 35 0.41 0.95
263 F -4 -4 -4 -2 -4 -4 -5 -5 0 -2 1 -5 -2 8 -5 -4 -4 -1 2 -3 0 0 0 2 0 0 0 0 2 0 16 0 0 71 0 0 0 0 4 0 1.51 1.00
264 H -2 -2 -2 -3 0 1 -3 -4 5 -3 -4 -3 -3 -2 7 -3 -3 -5 -1 1 3 2 2 0 2 6 0 0 15 0 0 0 0 2 52 0 0 0 2 12 1.24 1.00
265 C 1 -4 -3 -4 6 -3 -4 -4 2 3 -1 -4 -2 -3 -4 2 0 -4 -3 3 13 0 0 0 17 0 0 0 5 20 3 0 0 0 0 17 5 0 0 18 0.60 1.00
266 T 4 0 -3 -4 -3 -3 -3 0 -4 -4 -4 -3 -3 -4 -3 0 5 -4 1 -3 40 4 0 0 0 0 0 6 0 0 0 0 0 0 0 5 40 0 5 0 0.83 1.06
267 Q -1 0 0 0 2 2 -3 -4 -4 1 0 -3 1 -4 -4 2 3 4 -4 -1 5 6 4 5 4 11 0 0 0 8 9 0 4 0 0 15 18 6 0 4 0.34 1.22
268 Y -4 0 0 2 -5 0 0 -5 2 -4 -4 -4 -4 5 -5 -4 0 7 3 -1 0 5 5 13 0 5 7 0 5 0 0 0 0 23 0 0 6 16 11 5 0.81 1.22
269 I -3 -5 -5 -2 -4 -4 -5 -6 -5 6 2 -5 5 -3 -5 -4 -1 -5 -4 2 0 0 0 3 0 0 0 0 0 51 14 0 16 0 0 0 3 0 0 13 1.06 1.11
270 R -4 8 -3 -4 -6 -1 -3 -5 -3 -6 -5 0 -4 -6 -5 -3 -4 -5 -4 -5 0 100 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2.22 1.22
271 H -2 1 -1 -1 0 1 -1 -2 8 -5 -5 1 -4 -4 -1 0 1 -5 0 -2 2 8 3 3 2 5 3 3 41 0 0 7 0 0 3 7 8 0 2 2 0.89 1.22
272 G 0 2 -2 -2 0 -1 1 0 2 -1 -1 -1 0 -2 3 0 -2 1 -1 -1 6 14 2 2 2 2 8 8 6 3 5 4 2 2 17 8 2 2 2 5 0.23 1.22
273 S 0 -1 1 2 -5 0 4 -1 2 -5 -5 -1 -4 -2 -2 4 0 -6 -4 -5 5 2 6 12 0 2 24 3 4 0 0 3 0 2 2 29 5 0 0 0 0.59 1.31
274 K -1 -1 0 3 -1 3 3 -4 3 -5 -5 0 -1 -5 -4 2 -1 0 -2 -2 4 3 4 17 1 12 22 0 6 0 0 6 2 0 0 14 4 1 2 2 0.52 1.31
275 P -3 -4 -4 2 -4 -4 -2 -5 -4 2 1 -4 1 2 5 -3 -2 -4 -3 2 0 0 0 12 0 0 2 0 0 13 13 0 3 9 29 0 2 0 0 17 0.64 0.83
276 M -3 -1 2 5 -5 -1 2 0 0 -3 0 -2 3 0 -2 -1 -2 -4 -1 -4 1 4 8 33 0 1 13 7 2 0 10 1 9 4 1 2 1 0 2 0 0.47 0.83
277 Y -4 -4 -1 -5 -4 -3 -4 -5 5 -3 -2 -4 3 4 -5 -4 -4 -1 8 -3 0 0 3 0 0 0 0 0 14 0 0 0 10 18 0 0 0 0 55 0 1.40 0.83
278 T -1 -3 -1 -3 -3 -2 1 -3 -3 0 1 -3 -2 -4 -3 3 4 -5 -4 -1 4 0 2 0 0 0 10 0 0 7 14 0 0 0 0 28 33 0 0 3 0.52 0.83
279 P 0 0 -3 2 -4 2 0 -4 -3 -1 -2 -1 -3 -5 6 -2 -1 -5 -4 -1 7 5 0 13 0 12 6 0 0 4 4 3 0 0 38 0 3 0 0 4 0.77 0.83
280 E 0 -2 -2 0 -5 -1 6 -4 -2 -4 -1 0 -3 0 -3 -2 -1 -4 -3 -4 7 0 0 2 0 0 70 0 0 0 9 3 0 4 0 0 4 0 0 0 0.99 0.83
281 P -3 -4 -4 -3 -5 -3 0 -4 -3 -5 -5 -3 -4 -4 8 -3 -3 -4 2 -4 0 0 0 0 0 0 6 0 0 0 0 0 0 0 84 0 0 0 10 0 2.19 0.83
282 D 0 -3 3 7 -5 -2 -1 -3 -3 -5 -5 -2 -5 -5 2 -2 -3 -6 -5 -5 8 0 16 65 0 0 0 0 0 0 0 0 0 0 11 0 0 0 0 0 1.26 0.78
283 I -1 -4 -3 2 4 -3 -3 -2 -4 2 -1 -3 1 0 2 -1 2 -4 -1 1 3 0 0 16 10 0 0 3 0 15 5 0 4 4 11 3 13 0 3 12 0.34 0.78
284 C 1 -5 -5 -5 7 -4 -5 -4 -4 2 0 -4 -2 5 0 -3 -3 -3 -1 1 16 0 0 0 24 0 0 0 0 16 5 0 0 27 5 0 0 0 0 7 0.79 0.78
285 H -3 -2 -1 -3 -4 -1 -2 -4 9 -5 -4 -2 -3 -3 -4 1 2 -4 -1 -4 0 0 0 0 0 0 0 0 72 0 0 0 0 0 0 14 13 0 0 0 1.61 0.75
286 E -3 -3 -2 4 -5 -1 5 2 -3 -4 0 -1 -3 -4 -3 -2 -3 -5 -4 -4 0 0 0 23 0 0 47 14 0 0 13 1 0 0 0 0 0 0 0 0 0.80 0.75
287 L -1 -2 -3 -3 0 -2 -3 -2 -3 2 3 2 0 -1 -3 -1 -2 -3 -1 2 5 1 1 1 2 1 1 3 0 10 33 14 1 2 1 5 2 0 2 15 0.29 0.65
288 L 0 -3 -3 -4 -3 -3 -3 -3 -3 2 2 -3 0 6 -3 -2 -2 -2 1 0 9 1 1 1 0 1 1 1 0 10 23 1 2 39 1 2 1 0 2 4 0.62 0.65
289 G -1 -3 -2 -2 0 -2 -3 6 4 -4 -4 -3 -3 -3 -3 -2 -3 -3 -3 -4 3 1 1 1 3 1 1 69 14 1 1 1 0 1 1 1 1 0 0 1 1.15 0.65
290 H -3 -2 -1 -3 -3 -1 -2 -3 9 -3 1 -2 -2 -2 -3 -2 -3 -3 0 -3 1 1 1 1 0 1 1 1 72 1 15 1 0 1 1 1 1 0 0 1 1.48 0.65
291 V 1 -3 -3 -3 4 -3 -3 -1 -3 1 2 -3 3 -2 -3 -2 -1 -3 -3 4 14 1 1 1 9 1 1 5 0 4 17 1 7 1 1 2 3 0 0 33 0.39 0.65
292 P -1 -2 0 -3 5 -3 -3 2 -4 -2 -4 -3 -4 -5 7 -1 -3 -5 -5 -4 5 2 4 0 13 0 0 14 0 2 0 0 0 0 56 2 0 0 0 0 1.35 0.75
293 L -2 -4 -5 -5 3 -1 -4 -5 -4 2 3 -4 6 1 2 -4 -1 3 0 -1 3 0 0 0 6 3 0 0 0 10 29 0 22 5 10 0 3 4 3 3 0.64 1.00
294 F -3 -4 -5 -5 -4 -4 -5 -5 2 2 4 -4 2 2 -5 0 -3 -4 -2 1 0 0 0 0 0 0 0 0 5 11 53 0 5 10 0 10 0 0 0 6 0.76 1.00
295 S 3 -4 -4 -1 -3 -3 -4 -1 -4 0 1 -3 4 0 -4 0 1 -4 0 1 33 0 0 3 0 0 0 3 0 4 11 0 14 3 0 6 9 0 3 9 0.43 1.00
296 D -3 -3 5 5 -5 0 0 -3 4 -1 -5 -3 -4 -5 -4 1 -1 -5 -4 -4 0 0 30 34 0 3 5 0 9 4 0 0 0 0 0 10 2 0 0 0 0.94 1.12
297 R -1 1 -4 0 -6 1 -1 -1 -5 -1 -2 0 -4 -6 6 -1 -4 -6 -5 -1 5 8 0 5 0 6 4 5 0 4 4 6 0 0 44 5 0 0 0 4 0.89 1.61
298 S -1 1 1 2 -5 -1 1 -2 0 -2 -1 -1 0 -1 -1 2 0 2 0 -1 5 8 7 11 0 3 8 3 3 3 7 3 3 3 3 15 7 3 3 4 0.14 1.61
299 F -4 1 -5 -6 -5 -5 -5 -6 -3 0 -1 -4 1 7 -6 -4 -1 -2 5 -1 0 7 0 0 0 0 0 0 0 4 4 0 3 57 0 0 3 0 17 4 1.36 1.19
300 A 6 -4 -1 -4 2 -3 -4 -1 -4 -3 0 -3 1 -4 -4 0 -3 -5 -4 0 69 0 4 0 4 0 0 3 0 0 7 0 3 0 0 5 0 0 0 5 0.96 1.19
301 Q 0 1 2 1 -5 2 1 0 3 -5 -1 1 -4 -5 -4 1 1 -5 -4 -4 8 8 8 8 0 8 8 8 8 0 8 8 0 0 0 8 8 0 0 0 0.29 1.22
302 F -3 -5 -5 -6 -5 -5 -5 -6 0 0 0 -5 0 7 -1 -5 -2 -2 5 -1 2 0 0 0 0 0 0 0 2 4 8 0 2 54 4 0 3 0 18 4 1.32 1.36
303 S -1 -1 -1 -5 1 -4 -4 -5 -4 -1 1 -2 3 2 -2 2 3 -5 0 2 5 3 3 0 3 0 0 0 0 3 14 3 7 9 2 17 16 0 4 12 0.34 1.52
304 Q -1 2 -3 -4 0 5 1 -5 5 -2 -5 0 -4 -1 -5 -1 -1 2 0 -2 6 11 0 0 2 33 9 0 13 3 0 4 0 3 0 5 3 3 3 3 0.73 1.52
305 E -1 1 1 0 -5 1 0 -5 3 0 -1 0 2 1 -5 0 0 -5 2 0 6 6 6 6 0 6 6 0 6 6 6 6 6 6 0 6 6 0 6 6 0.18 1.67
306 I -2 -5 -5 -6 0 -5 -5 -1 -3 3 1 -5 1 4 -5 -3 -4 -2 6 -1 4 0 0 0 2 0 0 5 0 21 10 0 4 16 0 2 0 0 34 2 0.92 1.25
307 G 0 -5 -3 -4 3 -4 -1 7 -5 -6 -6 -4 -5 -6 -5 -1 -4 -5 -6 -5 6 0 0 0 6 0 5 79 0 0 0 0 0 0 0 5 0 0 0 0 1.60 1.25
308 L 0 2 -2 -2 2 2 2 -2 -4 -2 2 2 -1 -2 -2 -2 -3 -5 -4 -2 7 11 1 2 5 10 14 2 0 1 25 12 1 1 2 2 0 0 0 3 0.33 1.25
309 A 3 -4 -2 -5 1 -4 -4 0 -5 2 2 -1 0 -4 -4 -1 -1 -5 -4 1 31 0 1 0 2 0 0 6 0 11 22 5 2 0 0 5 3 0 0 11 0.45 1.25
310 S 2 0 -2 -4 -1 -4 -4 4 -4 -1 -3 -3 -4 0 -2 3 -3 -5 0 -1 15 6 1 0 1 0 0 36 0 4 2 0 0 4 1 21 0 0 3 5 0.58 1.25
311 L 0 1 -4 -5 1 -1 -3 -5 -4 0 4 -2 1 1 -4 -1 -2 0 -1 1 9 9 0 0 3 3 1 0 0 5 40 3 2 6 0 4 2 1 2 8 0.42 1.20
312 G 2 2 -1 -1 -2 0 -1 3 -1 -2 -4 3 -1 -5 -4 -1 1 -5 -4 -4 16 12 2 4 1 4 2 20 1 3 0 21 2 0 0 4 7 0 0 0 0.42 1.27
313 A 5 -4 -2 0 0 -1 0 -2 3 -2 -2 -3 -4 0 -4 -1 -1 -5 -2 -1 54 0 2 7 2 2 5 2 7 1 3 0 0 4 0 3 2 0 1 5 0.66 1.32
314 P -1 0 -1 1 1 0 2 -2 1 1 -2 -1 1 -1 0 1 1 2 -4 -2 5 4 3 8 3 4 14 3 4 7 4 3 4 3 5 13 7 3 0 3 0.15 1.67
315 D 0 1 0 3 -6 1 2 0 2 -6 -2 2 -5 -6 2 0 0 -6 -5 -5 6 7 4 15 0 5 14 8 4 0 4 12 0 0 10 5 5 0 0 0 0.38 1.67
316 E -1 -1 1 2 -5 0 4 2 -3 -5 -5 1 -5 -5 -3 1 -3 -6 -1 -2 4 3 5 12 0 4 27 18 0 0 1 8 0 0 1 12 0 0 2 3 0.53 1.43
317 Y 2 1 -2 4 -5 1 3 -3 -2 -1 -4 -2 0 -2 -4 -2 -2 -1 1 -1 19 6 1 22 0 6 20 2 1 3 1 1 3 1 0 2 1 1 5 6 0.45 1.43
318 I -3 2 -5 -5 0 -1 -5 -4 -4 4 3 -2 3 1 -5 -2 -2 1 -1 1 2 11 0 0 2 3 0 1 0 23 27 1 7 6 0 3 2 2 2 8 0.50 1.32
319 E 0 -1 -2 1 -5 2 3 -3 -1 -2 -2 2 -2 -5 0 1 -2 3 -4 -1 9 3 1 8 0 8 20 1 1 2 5 11 1 0 4 13 2 5 0 6 0.31 1.33
320 K 0 2 0 -4 -5 1 -1 -4 2 -4 1 3 1 2 -4 0 -2 3 1 -4 8 12 4 0 0 8 4 0 6 0 12 17 3 11 0 5 2 4 4 0 0.34 1.17
321 L -1 -4 -5 -6 -4 -4 -5 -5 -5 3 5 -1 2 1 -5 -4 -3 -4 -3 1 7 0 0 0 0 0 0 0 0 17 53 5 5 6 0 0 0 0 0 8 0.81 1.07
322 A 3 1 -4 -4 -4 1 -1 1 -4 -1 -1 -1 1 0 -1 1 0 -5 -4 -1 28 8 0 0 0 6 4 10 0 4 6 4 4 4 4 10 5 0 0 5 0.27 1.28
323 T -1 5 2 0 -5 2 -3 -1 2 -5 -5 1 -4 -5 -4 0 1 -5 -4 -1 5 38 8 5 0 8 0 5 5 0 0 6 0 0 0 6 10 0 0 5 0.65 1.28
324 I -3 -4 -5 -5 4 -4 -5 -5 -4 2 3 -4 3 3 1 -4 -1 -4 -2 2 0 0 0 0 11 0 0 0 0 9 31 0 9 12 8 0 4 0 0 15 0.61 0.81
325 Y 1 -3 0 -4 -4 -3 -3 -4 5 -3 -1 -3 -3 3 -4 -1 -3 4 7 -3 12 0 5 0 0 0 0 0 13 0 4 0 0 14 0 5 0 6 40 0 0.96 0.81
326 W -2 -4 -5 -5 1 1 -4 -4 -4 -3 -1 -4 1 2 1 -4 -4 11 0 -1 4 0 0 0 4 7 0 0 0 0 5 0 4 8 8 0 0 55 0 6 1.76 0.81
327 F -4 1 -4 -5 -4 -4 -4 -5 1 -2 0 -3 0 6 -5 -2 -3 5 5 -3 0 9 0 0 0 0 0 0 3 0 7 0 3 48 0 4 0 9 17 0 1.07 0.76
328 T 1 -3 -2 -3 1 -3 -3 -3 -4 -1 -3 -3 -2 -4 -3 2 6 -4 -3 1 11 0 0 0 3 0 0 0 0 3 0 0 0 0 0 13 61 0 0 9 0.84 0.76
329 V -1 -4 -4 -5 -3 0 -4 -5 -4 3 1 -4 2 0 -4 -3 -1 5 -2 5 4 0 0 0 0 5 0 0 0 15 9 0 6 3 0 0 2 8 0 48 0.69 0.71
330 E -2 -2 -2 0 -4 1 6 -3 -2 -4 -4 -1 -3 -4 -3 2 -2 -4 -3 -4 0 0 0 0 0 4 75 0 0 0 0 0 0 0 0 16 0 0 0 0 1.15 0.68
331 F -3 -4 -2 -4 1 -4 -4 -4 -2 -2 -2 -4 -2 7 -4 -2 -1 -1 4 -1 0 0 2 0 4 0 0 0 0 0 1 0 0 68 0 2 4 0 13 3 1.24 0.68
332 G -1 -3 -2 -2 -3 -3 -3 7 -3 -4 -4 -3 -4 -4 -3 -2 -3 -3 -4 -4 1 1 0 1 0 0 1 90 0 1 1 1 0 0 1 1 1 0 0 1 1.51 0.58
333 L 1 -3 -3 -3 -2 -2 -3 -3 -3 2 2 -3 4 -2 -3 -2 2 -3 -2 2 15 1 1 1 0 1 1 1 0 15 16 1 15 1 1 1 15 0 0 15 0.36 0.57
334 C -3 -4 -4 -4 7 -4 -4 -4 -4 3 1 -4 3 -3 -4 -1 0 -4 1 3 1 1 0 1 26 0 1 1 0 14 12 1 9 0 1 5 5 0 5 18 0.77 1.06
335 K 0 3 0 -1 0 1 -1 0 0 -2 -2 4 0 -3 -3 -1 -1 1 1 -2 7 15 4 4 2 7 4 7 2 3 3 26 2 0 1 3 3 2 5 3 0.31 1.06
336 Q -2 -1 0 0 -5 4 4 -2 0 -5 -5 1 -4 -6 -4 -1 3 -5 -4 -5 2 2 4 4 0 22 32 3 2 0 0 10 0 0 0 3 17 0 0 0 0.77 1.32
337 G -1 -1 3 3 -5 0 0 2 1 -2 -3 -1 -4 -5 2 -2 -2 -6 -5 -2 5 3 17 19 0 3 6 15 3 2 3 4 0 0 11 2 2 0 0 3 0.44 1.32
338 D -1 -4 2 2 -5 0 2 5 -1 -6 -6 -1 -5 -5 -2 -2 -2 4 -5 -5 4 0 10 12 0 4 12 43 1 0 0 3 0 0 2 2 1 6 0 0 0.82 1.32
339 S -1 0 1 0 -5 1 0 -1 2 0 -1 0 2 1 1 0 0 -6 -4 0 6 6 6 6 0 6 6 6 6 6 6 6 6 6 6 6 6 0 0 6 0.10 1.78
340 I -4 1 1 -4 3 1 -4 -5 -4 1 0 0 3 1 1 0 0 -4 2 0 0 7 7 0 7 7 0 0 0 7 7 7 7 7 7 7 7 0 7 7 0.27 1.44
341 K -2 5 -2 -2 1 0 2 -4 -2 -4 -4 5 -2 -5 -3 -2 -2 -5 -4 -3 1 30 1 0 3 2 12 0 0 0 0 47 1 0 0 1 1 0 0 1 0.92 0.77
342 A 4 -4 -4 -4 0 -3 -4 1 -4 4 -1 -3 0 -3 -4 -1 -2 -4 -4 1 44 0 0 0 2 0 0 13 0 26 3 0 2 0 0 1 0 0 0 10 0.60 0.77
343 Y -4 -4 2 -4 -1 -3 -4 -5 0 -2 -2 -4 -3 3 -5 -3 -3 0 8 -3 0 0 11 0 2 0 0 0 0 2 3 0 0 9 0 0 0 0 74 0 1.53 0.77
344 G -2 1 -2 -3 -5 -3 -4 7 -4 -6 -5 -3 -4 -5 -4 -2 -3 -4 -5 -5 0 11 0 0 0 0 0 89 0 0 0 0 0 0 0 0 0 0 0 0 1.64 0.77
345 A 5 2 -3 -3 -3 -2 -3 1 -3 -3 -4 -2 -3 -4 -3 2 -2 -5 -4 -1 58 15 0 0 0 0 0 11 0 0 0 0 0 0 0 13 0 0 0 3 0.74 0.75
346 G 0 -4 -2 2 -4 -3 -3 6 3 -5 -5 -3 -4 -5 -4 -1 -2 -5 -4 -3 6 0 0 13 0 0 0 66 8 0 0 0 0 0 0 2 2 0 0 2 1.11 0.75
347 L -1 -4 -5 -5 5 -4 -5 -5 -5 5 3 -4 3 -2 -5 -4 -3 -4 -3 1 3 0 0 0 13 0 0 0 0 38 32 0 8 0 0 0 0 0 0 6 0.84 0.75
348 L -1 -4 -4 -4 5 -3 -4 -4 -4 3 4 -4 1 -2 -4 -3 -2 -3 -3 2 4 0 0 0 13 0 1 1 0 22 41 0 2 0 0 1 0 0 0 11 0.68 0.68
349 S -1 -2 -1 -2 -3 -2 -2 0 4 -4 -4 -2 -3 -3 -2 5 1 -4 -2 -3 1 0 0 0 0 0 1 5 13 0 1 0 0 0 0 67 8 0 0 1 0.87 0.68
350 S 0 2 -1 -2 3 -2 -2 -1 -2 -4 -4 -1 -3 -4 -2 5 -1 -4 -3 -3 4 14 0 0 6 0 1 3 0 0 1 0 0 0 0 68 0 0 0 1 0.82 0.68
351 F -1 1 -2 -1 -1 -2 -2 -3 1 2 -2 -1 -2 1 3 1 -1 -3 3 -1 3 9 1 4 1 1 1 2 3 13 2 4 0 6 15 15 3 0 14 4 0.27 0.68
352 G -1 -1 1 0 -4 0 2 5 -1 -4 -4 1 -3 -4 -3 0 0 -4 -4 -4 5 2 7 4 0 3 15 42 1 1 1 9 0 0 1 5 4 0 0 1 0.58 0.71
353 E -2 -2 -2 -1 -4 1 6 -3 -2 -4 -4 -1 -3 0 -3 1 -2 -4 -3 -3 1 1 0 1 0 4 71 1 0 1 1 1 0 5 1 12 1 0 0 1 1.04 0.71
354 L 1 -3 -3 -3 6 -3 -3 -2 -3 -1 3 -3 0 -2 -3 1 1 -3 -3 -1 11 1 0 1 17 0 1 2 0 3 32 1 1 0 1 14 11 0 0 3 0.47 0.71
355 Q -2 3 -2 0 -2 1 1 -3 -1 -1 0 1 -1 -4 -2 0 2 -5 -4 1 2 16 1 5 1 6 11 1 1 3 11 10 1 0 1 8 13 0 0 9 0.23 0.88
356 Y -3 -3 -1 -2 -2 -1 0 -4 8 -5 -5 -4 -4 2 -5 -2 -4 2 7 -5 1 1 3 2 1 3 5 1 35 0 0 0 0 6 0 3 0 3 36 0 1.43 1.48
357 C 4 -5 -4 -5 6 -4 -4 -3 -5 -2 -3 -4 0 3 -4 2 -1 -5 -4 0 40 0 0 0 17 0 0 1 0 2 1 0 3 12 0 16 2 0 0 7 0.87 1.48
358 L -2 0 -5 -5 1 -3 -5 -6 0 1 4 -2 4 1 -5 -3 -1 -4 -1 1 2 6 0 0 3 1 0 0 2 6 42 2 10 7 0 2 4 0 2 10 0.62 1.44
359 S -1 -2 2 -1 -2 0 1 -2 -1 -4 -5 -1 -4 -5 -2 5 2 -5 -4 -3 2 1 9 3 1 3 8 2 1 1 1 4 0 0 1 50 11 0 0 1 0.73 1.40
360 E 1 -2 1 5 -5 0 0 3 -4 -5 -5 -2 -1 -5 2 -1 -2 -6 -5 -3 10 2 5 32 0 4 4 19 0 0 0 2 2 0 10 3 3 0 0 1 0.65 1.43
361 K 0 -1 1 1 -1 -1 2 -1 -1 0 -3 4 -2 -5 -1 0 0 -6 -5 -2 7 1 6 6 1 2 16 4 2 5 2 28 1 0 3 6 7 0 0 3 0.38 1.46
362 P 2 -5 -3 -2 2 -3 -1 -4 -5 -1 -3 -4 0 -5 6 -1 -2 -6 -5 2 21 0 1 2 4 1 4 0 0 2 2 0 2 0 41 3 1 0 0 16 0.96 1.45
363 K -3 1 3 -1 -1 1 4 -5 -1 -1 -2 3 -2 -2 0 -3 -2 -5 -4 -1 1 6 15 2 1 5 28 0 1 4 3 17 1 2 6 0 2 0 0 5 0.50 1.45
364 L -4 4 -4 -5 -2 -2 -4 -6 3 3 0 2 -1 1 -5 -4 -2 -5 2 2 0 22 0 0 1 1 0 0 7 20 7 13 1 6 0 0 3 0 6 14 0.59 1.48
365 L -3 4 -3 -3 -5 0 1 -4 0 2 1 2 0 0 -5 -2 -2 -5 0 0 1 24 1 1 0 4 9 1 2 12 12 15 2 4 0 3 1 0 3 7 0.43 1.48
366 P 0 1 -2 1 -6 -1 1 -1 -3 -4 -5 0 -2 -6 6 -2 -3 -1 -2 -4 7 7 1 8 0 2 8 5 1 1 1 6 1 0 46 2 1 1 1 1 0.99 1.48
367 L -5 -5 -6 -6 -5 -5 -6 -6 -1 -1 2 -6 0 8 -6 -4 -5 4 3 -3 0 0 0 0 0 0 0 0 1 2 18 0 2 61 0 1 0 6 8 0 1.63 1.48
368 E -3 -2 2 6 -6 -1 2 -3 -2 -4 -6 -1 -5 -6 -4 1 -1 -6 -5 -3 1 2 8 53 0 2 12 1 1 1 0 3 0 0 0 11 3 0 0 2 1.09 1.48
369 L -2 -5 -5 -5 -5 -5 -5 -6 -5 3 2 -5 1 -2 6 -4 -1 -6 -5 1 3 0 0 0 0 0 0 0 0 14 23 0 3 2 42 0 4 0 0 10 1.13 1.49
370 E 0 -2 -1 1 -2 1 4 -4 1 -1 -1 0 1 1 -3 0 -2 -5 -4 -1 8 2 3 8 1 5 30 1 3 4 7 5 3 7 1 5 1 0 0 5 0.34 1.43
371 K 1 2 -2 3 -5 0 0 -4 1 1 -2 1 -2 -4 -3 -1 1 -1 -4 1 13 13 1 16 0 4 6 0 3 7 3 8 1 1 1 4 9 1 0 10 0.27 1.46
372 T 3 -5 -4 -3 2 -4 -4 -5 0 2 -2 -3 2 -4 -1 -3 3 -6 -4 4 22 0 0 1 4 0 0 0 2 10 2 1 6 0 2 0 22 0 0 27 0.65 1.47
373 A 3 -1 -5 -5 5 -2 -5 0 -5 1 2 -4 5 -1 -5 -1 -2 -5 -4 -1 24 3 0 0 11 2 0 7 0 9 18 0 15 2 0 4 1 0 0 3 0.57 1.46
374 I -3 4 2 2 -2 1 0 -3 -1 -3 -2 1 -3 -3 -1 -3 0 -6 -2 0 1 26 8 12 1 6 6 1 1 1 5 9 1 1 4 1 6 0 2 8 0.40 1.47
375 Q -3 2 -3 -4 -5 5 1 -5 -1 -2 -3 0 0 -5 -4 -2 5 -5 -2 -2 1 9 0 0 0 30 7 0 1 2 2 4 2 0 0 1 39 0 1 2 0.91 1.47
376 N -2 0 -1 1 -6 -2 3 -4 0 -5 -4 2 1 -6 5 -1 -1 -6 -5 -2 3 5 3 8 0 1 21 1 2 0 1 11 4 0 30 4 4 0 0 3 0.73 1.47
377 Y -2 -5 -5 -6 5 -4 -5 -4 -1 -2 -4 -5 -4 3 -4 -2 -4 -1 8 -2 2 0 0 0 13 1 0 1 1 2 0 0 0 11 1 3 0 0 64 2 1.76 1.47
378 T -3 4 0 4 -6 1 0 -4 -1 0 -2 -1 -3 -5 3 -1 -3 -3 0 -2 2 22 3 21 0 7 4 0 2 7 4 3 0 0 14 3 1 0 4 2 0.51 1.48
379 V -3 -5 -5 2 -4 -5 -5 -6 -6 7 -1 0 -2 -3 -1 -4 -1 -6 -3 1 1 0 0 11 0 0 0 0 0 63 3 6 0 1 3 0 4 0 1 8 1.12 1.48
380 T -3 -4 0 5 -3 2 -1 -3 -3 -5 -4 -3 -4 -4 -4 0 5 -2 -1 -3 0 0 3 32 0 10 2 2 0 0 1 0 0 1 0 4 40 1 2 1 0.96 1.48
381 E -1 0 -1 0 -2 0 1 0 2 2 -4 2 -2 -5 -4 1 3 -6 -4 -3 5 4 3 6 1 4 10 7 6 13 0 12 1 0 0 9 18 0 0 1 0.32 1.48
382 F -4 -5 -1 -6 -5 -3 -4 -6 -3 -1 0 -4 5 5 0 -4 -3 -2 6 -1 0 0 3 0 0 0 1 0 0 3 8 1 17 23 5 0 1 0 34 3 1.13 1.43
383 Q -3 -2 -2 -3 -5 8 -1 -4 4 -5 -5 -1 -3 -5 2 -3 -3 -5 -3 -5 0 0 0 0 0 76 0 0 12 0 0 0 0 0 12 0 0 0 0 0 1.62 1.04
384 P -1 -1 1 1 -5 1 4 -4 1 -5 -3 1 -4 -5 4 -1 -1 -5 -4 -4 3 3 7 5 0 6 32 0 3 0 3 8 0 0 23 4 3 0 0 0 0.70 1.04
385 L 0 -1 3 -1 0 0 -1 0 3 0 -2 -1 0 -4 -4 -1 3 -5 -4 1 10 3 14 2 2 4 3 7 8 5 3 3 2 0 0 3 20 0 0 12 0.27 1.04
386 Y -4 -4 -5 -5 -4 -4 -4 -5 -1 -2 2 -4 -2 3 -5 -4 -4 0 8 -3 0 0 0 0 0 0 0 0 0 0 22 0 0 10 0 0 0 0 67 0 1.52 0.83
387 Y -4 -4 -5 -5 1 -5 -5 -5 -2 -2 -1 -5 1 7 -5 -4 -4 4 5 -3 0 0 0 0 3 0 0 0 0 0 3 0 4 67 0 0 0 5 18 0 1.49 0.78
388 V 0 -3 -5 -5 0 -4 -2 -5 -4 2 -1 -4 0 -2 -5 -2 -1 -4 4 5 6 1 0 0 2 0 3 0 0 9 3 0 2 0 0 2 3 0 15 56 0.86 1.10
389 A 2 -4 -4 -4 2 -4 -4 -4 -4 4 1 -4 -2 0 -4 1 2 -4 -3 0 18 0 0 0 4 0 0 0 0 27 15 0 0 4 0 10 16 0 0 4 0.50 1.06
390 E -3 0 1 5 -5 -1 4 -3 -1 -5 -5 0 -4 -5 2 -1 -2 -5 -4 -5 1 6 7 32 0 2 28 1 1 0 0 3 0 0 11 4 2 0 0 0 0.80 1.06
391 S -1 -3 1 3 -4 -1 -1 -1 0 -5 -5 -1 -4 -5 -3 6 0 -5 -4 -4 1 0 5 15 0 1 2 4 3 0 0 2 0 0 0 63 3 0 0 0 0.93 1.06
392 F -4 -5 -5 -5 0 -5 -5 -5 -4 2 2 -5 0 7 -5 -4 -3 -2 2 -1 0 0 0 0 2 0 0 0 0 10 20 0 2 52 0 0 1 0 6 4 1.16 1.06
393 N 0 -1 -1 3 -2 1 4 -2 -1 -4 -3 1 -4 -3 -2 1 -1 -5 -4 -3 8 2 2 18 1 6 34 2 1 0 2 9 0 1 1 10 2 0 0 1 0.56 1.05
394 D -2 -1 -1 4 -5 3 3 -4 4 -3 -4 0 -2 -1 -3 -1 -1 -4 0 -4 3 3 1 21 0 16 23 0 10 1 0 5 1 3 0 5 3 0 3 1 0.60 1.05
395 A 3 -4 -4 -5 2 -4 -4 -3 -4 0 4 -4 3 -3 -4 -2 -3 -4 -3 0 27 0 0 0 4 0 0 2 0 3 50 0 6 0 0 1 0 0 0 4 0.74 1.05
396 K -2 0 -2 0 -4 0 0 -4 -2 0 0 3 0 3 -4 0 -1 -3 2 -2 3 5 1 6 0 3 6 1 1 6 10 23 3 14 0 6 4 0 8 2 0.29 1.08
397 E -1 0 0 4 -3 3 5 -3 -1 -3 -3 0 -4 -5 -4 0 -2 -5 -3 -3 4 6 3 23 0 11 35 1 1 1 2 3 0 0 0 7 1 0 1 1 0.72 1.13
398 K 0 0 -2 -1 -4 1 -1 -4 -4 3 1 4 -1 -4 -2 -1 -2 -5 -4 2 6 4 1 4 0 5 4 1 0 17 12 25 1 0 1 3 1 0 0 14 0.35 1.12
399 V 1 -4 -4 -4 0 -3 -3 -4 -4 0 3 -4 5 2 -4 -1 0 -4 -3 1 12 0 0 0 1 0 2 1 0 4 33 0 16 7 0 6 6 0 0 10 0.52 1.10
400 R -1 5 -1 1 -5 1 2 -1 1 -1 -4 2 -2 -4 -2 -2 -3 -4 0 -2 4 33 2 9 0 6 12 5 3 5 1 9 1 0 1 2 1 0 4 2 0.50 1.12
401 N 0 0 0 1 -2 2 3 -1 -3 -1 -2 2 3 -4 -3 0 1 -1 -2 -1 9 5 3 7 1 8 18 4 0 3 4 11 7 0 0 7 7 1 1 3 0.23 1.14
402 F -3 -4 -3 3 -4 -3 -3 -4 -3 0 0 -4 0 6 -4 -3 -3 4 4 -3 2 1 0 19 0 0 1 1 0 4 8 1 2 36 1 1 1 5 17 1 0.90 1.09
403 A 4 -3 -3 -3 0 -2 -1 0 -2 2 1 -3 0 0 -3 -1 -1 2 -3 0 34 1 0 1 2 2 4 6 1 13 12 1 2 4 1 4 4 3 0 6 0.35 1.10
404 A 2 0 2 1 -2 1 1 -1 -2 -3 -2 1 5 -4 -3 0 -2 -4 -4 -3 21 4 8 7 1 5 11 4 1 1 2 10 15 0 0 8 1 0 0 1 0.36 1.14
405 T 1 0 -1 -2 -4 2 -2 -1 1 -3 0 1 -2 -3 -2 2 4 -2 -3 -3 12 6 3 2 0 8 2 5 3 0 9 7 1 1 1 14 25 1 0 0 0.32 1.17
406 I 0 -3 -4 -5 -1 -2 -3 -1 -4 4 2 -3 6 0 -4 -3 -1 -4 -1 0 7 1 0 0 1 1 1 4 0 27 21 1 19 3 0 2 3 0 2 5 0.59 1.17
407 P -1 -1 -2 0 0 3 0 -2 1 -2 -1 2 -3 -3 3 -1 -2 -5 -2 1 5 3 2 6 2 15 6 3 3 2 5 13 0 1 13 4 2 0 1 13 0.26 1.21
408 R 0 6 -3 0 -4 -1 -1 -2 0 -1 -1 3 -3 -4 -1 -3 -1 -5 -4 -3 7 40 0 4 0 2 2 2 2 5 7 18 0 0 3 0 4 0 0 2 0.65 1.20
409 P -3 -1 -2 4 -5 1 2 -4 -4 -4 -3 -1 -4 -6 6 -2 -3 -6 -5 -5 1 3 1 23 0 5 12 1 0 1 3 3 0 0 45 3 0 0 0 0 1.19 1.24
410 F -3 -5 -3 -3 -5 -5 -4 -5 2 -3 0 -5 0 8 -4 -2 -2 -2 0 -3 1 0 1 2 0 0 1 0 6 0 6 0 2 73 1 3 3 0 1 1 1.55 1.22
411 S 3 -3 -2 -1 -4 -1 1 2 -1 0 -3 -1 -2 -3 0 2 0 -5 -3 -2 25 1 1 4 0 2 11 15 1 6 1 3 1 1 5 13 6 0 1 2 0.31 1.27
412 V -1 -3 -5 -3 -1 -4 -4 -4 -5 0 0 -4 -3 -3 6 -3 0 -5 -4 4 5 1 0 1 1 0 0 1 0 4 11 1 0 1 37 1 5 0 0 30 0.93 1.27
413 R -1 5 -2 -2 0 -3 -3 -5 1 0 1 2 -1 -3 -4 -3 -1 1 1 -1 5 31 1 2 2 0 0 0 3 5 17 13 1 0 0 1 4 2 5 5 0.48 1.27
414 Y -4 -4 -3 -3 -5 -4 -3 -2 1 -3 -3 -4 -3 5 -5 -4 -4 -1 8 -4 0 0 1 1 0 0 1 3 3 0 1 0 0 26 0 0 0 0 61 0 1.72 1.23
415 D 0 -2 4 5 -5 1 2 -4 -3 -5 -5 -2 -4 -5 2 -2 -1 -6 -5 -5 8 1 25 30 0 7 12 0 0 0 1 1 0 0 12 0 3 0 0 0 0.85 1.23
416 P 0 0 -1 -3 -5 -2 -2 -4 -2 -4 -4 -2 -4 0 7 -1 -3 -6 -4 -2 9 6 3 0 0 1 2 0 1 1 1 1 0 5 63 4 0 0 0 2 1.50 1.24
417 Y 0 -2 -2 -2 -5 -2 0 -4 1 -1 0 3 -2 1 -4 -3 -2 -2 6 -2 8 1 2 2 0 1 7 1 3 4 11 18 0 6 1 1 2 0 33 1 0.62 1.24
418 T 0 -2 -2 -2 -4 -2 0 -4 1 -2 -3 -2 -3 -1 -2 0 6 -4 3 -2 9 2 1 2 0 1 5 0 3 1 2 1 0 2 2 5 50 0 11 1 0.72 1.25
419 Q 1 1 -2 0 -1 5 2 0 -1 -5 -2 2 -2 -5 -2 -1 -3 -5 -4 -4 12 6 1 4 1 31 13 6 1 0 5 14 1 0 2 3 0 0 0 0 0.56 1.25
420 R 3 1 -1 -1 -1 0 -1 -2 -4 -3 -4 -2 -3 -5 -2 4 3 -5 -4 -3 25 7 2 2 1 5 3 1 0 1 1 1 0 0 2 31 16 0 0 1 0.56 1.24
421 I 0 -4 -2 -2 -4 -4 -4 2 -5 4 0 -3 -2 -3 -2 -2 -1 -5 -4 4 7 0 2 2 0 0 0 16 0 24 6 1 0 0 2 3 3 0 0 32 0.55 1.16
422 E 1 -3 -1 4 -3 1 5 -4 3 -3 -4 -1 -4 -5 -3 -2 -2 -5 -4 -3 12 0 1 21 1 5 42 0 6 2 1 2 0 0 0 2 2 0 0 1 0.80 1.12
423 V 0 -4 -5 -5 -3 -3 -4 -3 -5 4 0 -3 1 -3 -3 -3 -2 -5 -3 6 6 0 0 0 0 1 0 2 0 20 5 2 2 0 1 0 2 0 0 58 0.93 1.10
424 L -1 -4 -5 -5 -4 -2 -5 -5 -5 2 5 -3 0 -1 -5 -2 -2 -4 -3 0 4 0 0 0 0 2 0 0 0 10 70 2 1 2 0 4 2 0 0 3 0.96 1.15
425 D -2 -2 0 6 -5 -2 1 -3 -4 -5 -5 1 -2 -6 3 0 0 -6 -4 -5 3 2 4 42 0 1 6 1 0 0 0 10 1 0 17 5 6 0 1 0 0.86 1.19
426 N -1 -2 2 2 -2 -1 0 2 -1 -5 -5 -1 -4 -3 -2 3 2 -5 -3 -2 3 2 12 12 1 2 6 13 2 0 0 3 0 1 2 26 14 0 1 3 0.44 1.19
427 T -2 -2 -2 5 -5 -1 -1 -4 -4 0 -2 1 -1 -2 2 -2 2 -6 -5 0 3 2 1 37 0 2 3 0 0 5 3 9 1 2 10 2 11 0 0 9 0.56 1.20
428 Q -1 5 -1 1 -4 3 0 -2 2 -4 -3 1 -4 -3 0 -1 -2 -5 -2 -2 5 32 2 7 0 11 6 3 6 1 3 9 0 1 5 5 1 0 1 2 0.50 1.20
429 Q 1 0 -2 -1 -3 2 -3 -3 -2 0 -3 2 0 -4 -4 1 -2 -5 -4 4 12 5 1 3 0 10 0 1 1 4 0 16 2 0 0 13 1 0 0 31 0.44 1.19
430 L -3 -2 -2 -5 -4 -4 -3 -3 -5 5 3 -3 1 0 -5 -4 -3 -4 -1 2 1 2 2 0 0 0 2 2 0 34 32 1 2 4 0 0 0 0 2 15 0.75 1.19
431 K 0 0 2 -2 0 3 1 -4 2 -2 -3 2 -1 -5 -1 -1 3 -5 -4 -2 9 4 9 2 2 13 9 0 6 3 2 11 2 0 3 2 24 0 0 2 0.39 1.20
432 I 0 5 2 0 -3 -1 0 -2 1 -2 -1 -1 -2 -2 -4 0 1 -5 -4 -1 6 32 12 6 0 1 5 2 3 2 6 2 1 1 0 6 8 0 0 5 0.41 1.20
433 L 0 -5 -4 -5 -2 -4 -4 4 1 -2 3 -4 -1 -2 -5 0 -3 -5 -4 1 9 0 0 0 1 0 1 36 4 1 28 0 1 1 0 7 1 0 0 12 0.63 1.20
434 A 1 -4 -2 -3 -2 -4 -3 -3 -5 0 2 -4 1 -1 -1 0 4 -5 -3 2 10 0 1 1 1 0 1 1 0 5 19 0 3 2 3 6 31 0 1 17 0.48 1.20
435 D -1 3 2 0 -3 3 1 3 1 -5 -5 0 -4 -5 -4 1 -2 -2 -3 -5 3 14 11 5 1 15 10 20 3 1 0 5 0 0 0 10 1 1 1 0 0.50 1.19
436 S -3 0 2 3 -2 2 5 -2 1 -5 -5 0 -4 -5 -4 0 -1 -3 -4 -3 1 4 10 17 1 9 36 3 4 0 0 3 0 0 0 8 4 0 0 1 0.69 1.13
437 I -3 -4 -5 -5 -3 -4 -5 -6 -4 4 3 -4 3 0 -5 -4 0 -4 2 3 0 0 0 0 0 0 0 0 0 24 34 0 6 2 0 0 5 0 7 22 0.76 0.93
438 N -3 4 3 -1 -5 3 -1 -3 2 -5 -5 4 -4 -5 -4 1 -2 -5 -4 -5 0 22 17 3 0 16 1 0 5 0 0 24 0 0 0 11 0 0 0 0 0.77 0.92
439 S -1 -3 1 2 -3 0 2 2 4 -4 -1 -3 -3 -2 -4 2 0 -5 -2 -3 3 0 7 11 0 4 12 18 11 1 6 0 0 2 0 17 6 0 1 1 0.37 0.91
440 E -1 -3 0 4 -5 1 5 -1 -2 -5 -5 -2 1 -5 -3 -2 -3 -5 -3 -4 5 0 3 27 0 5 50 5 0 0 0 0 4 0 0 0 0 0 1 0 0.98 0.89
441 I -1 -4 -5 -5 -3 -4 -5 -5 -5 2 4 -4 4 1 -5 -3 -2 -4 -3 2 5 0 0 0 0 0 0 0 0 13 49 0 13 7 0 1 1 0 0 12 0.80 0.89
442 G -2 -2 3 2 1 2 0 0 2 -4 -2 0 -3 -5 -4 2 0 -5 -4 -2 2 1 16 14 4 12 3 8 4 0 4 6 0 0 0 18 5 0 0 3 0.37 0.89
443 I 0 -4 0 -4 -3 0 -3 -4 4 4 0 -2 -1 -3 -4 0 2 -5 -3 1 9 0 4 0 0 4 0 0 11 32 7 1 1 0 0 7 15 0 0 9 0.47 0.89
444 L -3 -4 -5 -5 -3 -4 -1 -6 -5 2 5 -4 1 0 -5 -4 0 -4 -3 2 0 0 0 0 0 0 4 0 0 10 61 0 2 3 0 0 5 0 0 14 0.83 0.89
445 C 0 -2 1 0 5 1 -1 0 -1 -2 -3 -1 1 -3 -4 2 3 -5 -4 -1 7 1 7 4 13 5 4 7 2 1 1 4 3 1 0 14 23 0 0 3 0.37 0.89
446 S -2 -3 4 4 0 -1 1 -2 3 -4 -3 -1 -4 -3 -4 1 2 -5 -1 -3 2 0 21 26 2 2 7 2 7 0 2 3 0 1 0 10 12 0 2 1 0.56 0.89
447 A 6 -4 -3 -4 -3 -3 -3 -2 -4 -3 -1 -3 -3 1 -3 1 -1 -4 -3 -1 77 0 0 0 0 0 0 0 0 0 4 0 0 6 0 8 2 0 0 2 0.97 0.85
448 L 0 -4 -5 -5 -3 -4 -5 -5 -5 1 5 -4 2 0 -5 -4 -3 -4 -3 1 9 0 0 0 0 0 0 0 0 6 71 0 5 2 0 0 0 0 0 7 0.94 0.85
449 Q 0 1 3 1 -2 0 2 0 0 -5 -3 2 -4 -5 -3 2 -2 -5 -4 -3 6 9 18 8 1 3 15 8 2 0 2 12 0 0 0 15 1 0 0 1 0.39 0.85
450 K 0 3 -1 -3 -5 0 -1 -4 -3 -4 -4 6 -2 -5 -3 -1 -1 -5 -1 -1 6 12 2 0 0 1 2 0 0 0 0 66 1 0 0 2 2 0 2 5 0.95 0.83
451 I -3 -4 -5 -4 -1 -4 -5 -5 -5 4 4 -4 6 -1 -5 -4 -3 -4 -3 1 0 0 0 1 1 0 0 0 0 32 39 0 23 1 0 0 0 0 0 4 0.95 0.83
452 K -2 2 -2 -2 -5 4 2 -3 -2 -4 -4 5 -3 -5 -3 -2 -2 -4 -3 -4 0 11 0 0 0 24 10 0 0 0 0 55 0 0 0 0 0 0 0 0 0.91 0.53

MSA with all mammalian homologous

We identified homologous sequences from mammalians with the help of HSSP. We used the entry 1J8U. Then we checked whether the homologous sequences of this entry are from mammalians and whether they are not only a "Fragment". The reason for this is that fragment sequences are very short and may not be very helpful for our alignment. The following entries fulfilled these requirements:

FASTA Header
PDBID|CHAIN|SEQUENCE
P00439|PH4H_HUMAN Phenylalanine-4-hydroxylase OS=Homo sapiens GN=PAH PE=1 SV=1
Q16265|Q16265_HUMAN PAH protein (Fragment) OS=Homo sapiens GN=PAH PE=4 SV=1
Q16021|Q16021_HUMAN PAH protein (Fragment) OS=Homo sapiens GN=PAH PE=2 SV=2
Q8TEY0|Q8TEY0_HUMAN Phenylalanine hydroxylase OS=Homo sapiens GN=PAH PE=2 SV=1
Q16266|Q16266_HUMAN PAH protein (Fragment) OS=Homo sapiens GN=PAH PE=4 SV=1
Q91WV1|Q91WV1_MOUSE Phenylalanine hydroxylase OS=Mus musculus GN=Pah PE=2 SV=1
B2R8I4|B2R8I4_HUMAN cDNA, FLJ93916, highly similar to Homo sapiens phenylalanine hydroxylase (PAH), mRNA OS=Homo sapiens PE=2 SV=1
Q8TEY0|Q8TEY0_HUMAN Phenylalanine hydroxylase OS=Homo sapiens GN=PAH PE=2 SV=1
Q5RDX0|Q5RDX0_PONAB Putative uncharacterized protein DKFZp469G0337 OS=Pongo abelii GN=DKFZp469G0337 PE=2 SV=1
E2R3S1|E2R3S1_CANFA Uncharacterized protein OS=Canis familiaris GN=PAH PE=4 SV=1
E2R366|E2R366_CANFA Uncharacterized protein OS=Canis familiaris GN=PAH PE=4 SV=1
Q91WV1|Q91WV1_MOUSE Phenylalanine hydroxylase OS=Mus musculus GN=Pah PE=2 SV=1
Q3UEH8|Q3UEH8_MOUSE Putative uncharacterized protein OS=Mus musculus GN=Pah PE=2 SV=1
P16331|PH4H_MOUSE Phenylalanine-4-hydroxylase OS=Mus musculus GN=Pah PE=1 SV=3
Q2KIH7|PH4H_BOVIN Phenylalanine-4-hydroxylase OS=Bos taurus GN=PAH PE=2 SV=1
D3Z270|D3Z270_MOUSE Uncharacterized protein OS=Mus musculus GN=Pah PE=4 SV=1
P04176|PH4H_RAT Phenylalanine-4-hydroxylase OS=Rattus norvegicus GN=Pah PE=1 SV=3
Q8HXR0|Q8HXR0_MACMU Tryptophan hydroxylase (Fragment) OS=Macaca mulatta GN=TPH PE=2 SV=1
Q6AYW2|Q6AYW2_RAT Phenylalanine hydroxylase OS=Rattus norvegicus GN=Pah PE=2 SV=1
B4DPN2|B4DPN2_HUMAN cDNA FLJ56667, highly similar to Phenylalanine-4-hydroxylase (EC 1.14.16.1) OS=Homo sapiens PE=2 SV=1
Q14CC5|Q14CC5_HUMAN TPH2 protein OS=Homo sapiens GN=TPH2 PE=2 SV=1
Q8IWU9|TPH2_HUMAN Tryptophan 5-hydroxylase 2 OS=Homo sapiens GN=TPH2 PE=1 SV=1
Q2HZ26|TPH2_MACMU Tryptophan 5-hydroxylase 2 OS=Macaca mulatta GN=TPH2 PE=2 SV=1
Q8CGU9|TPH2_RAT Tryptophan 5-hydroxylase 2 OS=Rattus norvegicus GN=Tph2 PE=2 SV=1
P17752|TPH1_HUMAN Tryptophan 5-hydroxylase 1 OS=Homo sapiens GN=TPH1 PE=1 SV=4
Q86Y20|Q86Y20_HUMAN Tryptophan hydroxylase (Fragment) OS=Homo sapiens PE=2 SV=1
Q86WC5|Q86WC5_HUMAN Tryptophan hydroxylase (Fragment) OS=Homo sapiens PE=2 SV=1
Q86Y19|Q86Y19_HUMAN Tryptophan hydroxylase (Fragment) OS=Homo sapiens PE=2 SV=1
Q9JHZ8|Q9JHZ8_MOUSE Tryptophan hydroxylase (Fragment) OS=Mus musculus GN=Tph1 PE=2 SV=1
Q8K3R1|Q8K3R1_MESAU Tryptophane hydroxylase OS=Mesocricetus auratus PE=2 SV=1
E1BGX6|E1BGX6_BOVIN Uncharacterized protein OS=Bos taurus GN=TPH2 PE=4 SV=1
Q0EAB8|TPH2_HORSE Tryptophan 5-hydroxylase 2 OS=Equus caballus GN=TPH2 PE=2 SV=1
Q0VBT4|Q0VBT4_MOUSE Tryptophan hydroxylase 2 OS=Mus musculus GN=Tph2 PE=2 SV=1
B6EY10|B6EY10_CANFA Tryptophan hydroxylase 1 isoform 1 OS=Canis familiaris GN=TPH1 PE=2 SV=1
Q8CGV2|TPH2_MOUSE Tryptophan 5-hydroxylase 2 OS=Mus musculus GN=Tph2 PE=2 SV=1
P09810|TPH1_RAT Tryptophan 5-hydroxylase 1 OS=Rattus norvegicus GN=Tph1 PE=2 SV=2
P17290|TPH1_RABIT Tryptophan 5-hydroxylase 1 OS=Oryctolagus cuniculus GN=TPH1 PE=1 SV=2
P17532|TPH1_MOUSE Tryptophan 5-hydroxylase 1 OS=Mus musculus GN=Tph1 PE=2 SV=1
Q3UK52|Q3UK52_MOUSE Tryptophan hydroxylase 1 OS=Mus musculus GN=Tph1 PE=2 SV=1
Q76IQ3|TY3H_CANFA Tyrosine 3-monooxygenase OS=Canis familiaris GN=TH PE=2 SV=1
P04177|TY3H_RAT Tyrosine 3-monooxygenase OS=Rattus norvegicus GN=Th PE=1 SV=3
Q8IZE2|Q8IZE2_HUMAN Putative tyrosine hydroxylase variant (Fragment) OS=Homo sapiens PE=2 SV=1
Q8IZE1|Q8IZE1_HUMAN Truncated tyrosine hydroxylase (Fragment) OS=Homo sapiens PE=2 SV=1
Q8N1X9|Q8N1X9_HUMAN cDNA FLJ37295 fis, clone BRAMY2015311, moderately similar to TRYPTOPHAN 5-MONOOXYGENASE (EC 1.14.16.4) OS=Homo sapiens PE=2 SV=1
Q8MJD2|Q8MJD2_RABIT Tyrosine hydroxylase (Fragment) OS=Oryctolagus cuniculus PE=2 SV=1
Q8HY50|Q8HY50_RABIT Tyrosine hydroxylase (Fragment) OS=Oryctolagus cuniculus PE=2 SV=1
Q95LQ6|Q95LQ6_HORSE Tyrosine hydroxylase (Fragment) OS=Equus caballus GN=TH PE=2 SV=1
Q8HZ55|Q8HZ55_PANTR Tyrosine hydroxylase (Fragment) OS=Pan troglodytes PE=4 SV=1
Q8HZ54|Q8HZ54_9PRIM Tyrosine hydroxylase (Fragment) OS=Gorilla gorilla PE=4 SV=1
Q8MIU1|Q8MIU1_PIG Tyrosine hydroxylase (Fragment) OS=Sus scrofa PE=4 SV=1
Q8HZ53|Q8HZ53_PONPY Tyrosine hydroxylase (Fragment) OS=Pongo pygmaeus PE=4 SV=1
Q8HXJ0|Q8HXJ0_MACFA Putative uncharacterized protein OS=Macaca fascicularis PE=2 SV=1
P97517|P97517_PHOSU Tyrosine hydroxylase (Fragment) OS=Phodopus sungorus PE=2 SV=1
P07101|TY3H_HUMAN Tyrosine 3-monooxygenase OS=Homo sapiens GN=TH PE=1 SV=5
Q2M3B4|Q2M3B4_HUMAN Tyrosine hydroxylase OS=Homo sapiens GN=TH PE=2 SV=1
B6EY12|B6EY12_CANFA Tryptophan hydroxylase 2 OS=Canis familiaris GN=TPH2 PE=2 SV=1
B7ZL73|B7ZL73_HUMAN TH protein OS=Homo sapiens GN=TH PE=2 SV=1
E0V877|E0V877_MICOH Tyrosine hydroxylase OS=Microtus ochrogaster GN=TH PE=4 SV=1
Q3UTB3|Q3UTB3_MOUSE Putative uncharacterized protein OS=Mus musculus GN=Th PE=2 SV=1
Q76IQ3|TY3H_CANFA Tyrosine 3-monooxygenase OS=Canis familiaris GN=TH PE=2 SV=1
Q8K3R1|Q8K3R1_MESAU Tryptophane hydroxylase OS=Mesocricetus auratus PE=2 SV=1
P24529|TY3H_MOUSE Tyrosine 3-monooxygenase OS=Mus musculus GN=Th PE=1 SV=3
B3RFH4|B3RFH4_SORAR Tyrosine 3-monooxygenase (Predicted) OS=Sorex araneus GN=TH PE=4 SV=1
B7NZU5|B7NZU5_RABIT Tyrosine hydroxylase isoform b (Predicted) OS=Oryctolagus cuniculus GN=TH PE=4 SV=1
Q0PWM3|Q0PWM3_HUMAN Tyrosine hydroxylase isoform D1b,2,8,9 OS=Homo sapiens GN=TH PE=2 SV=1
Q0PWM2|Q0PWM2_HUMAN Tyrosine hydroxylase isoform D2,8,9 OS=Homo sapiens GN=TH PE=2 SV=1
B2KIN8|B2KIN8_RHIFE Tyrosine hydroxylase (Predicted) OS=Rhinolophus ferrumequinum GN=TH PE=4 SV=1
P17289|TY3H_BOVIN Tyrosine 3-monooxygenase OS=Bos taurus GN=TH PE=1 SV=5
Q8HXJ0|Q8HXJ0_MACFA Putative uncharacterized protein OS=Macaca fascicularis PE=2 SV=1
B6EY11|B6EY11_CANFA Tryptophan hydroxylase 1 isoform 2 OS=Canis familiaris GN=TPH1 PE=2 SV=1
Q3TZH2|Q3TZH2_MOUSE Putative uncharacterized protein OS=Mus musculus GN=Tph1 PE=2 SV=1
Q8N1X9|Q8N1X9_HUMAN cDNA FLJ37295 fis, clone BRAMY2015311, moderately similar to TRYPTOPHAN 5-MONOOXYGENASE (EC 1.14.16.4) OS=Homo sapiens PE=2 SV=1
Q08EN2|Q08EN2_HUMAN TPH1 protein OS=Homo sapiens GN=TPH1 PE=2 SV=1


After we had all our FASTA sequences we used t-coffee 3D to create our MSA. We utilized the following command to create our MSA with the structure of 1J8U as reference:

  • t_coffee ../homo_seq.fasta -method sap_pair,slow_pair -template_file 1J8U

The resulting MSA is as follows:

T coffee homo ali pah.png

I65T

Figure 3. Histogram of PSI-Blast PSSM conservation scores for position 65

Substitution Scores:
Blosum 62: -1
PAM 1: 11
PAM 250: 6
PSI-PSSM: 6 I
PSI-PSSM: -4 T
Multiple Alignment: 1/74 I
Multiple Alignment: 0/74 T

R71H

Figure 3. Histogram of PSI-Blast PSSM conservation scores for position 71

Substitution Scores:
BLOSUM62: 0
PAM1: 10
PAM250: 5
PSI-PSSM: -2 R
PSI-PSSM: -2 H
Multiple Alignment: 1/74 R
Multiple Alingment: 0/74 H

R158Q

Figure 3. Histogram of PSI-Blast PSSM conservation scores for position 158

Substitution Scores:
BLOSUM62: 1
PAM1: 9
PAM250: 5
PSI-PSSM: 6 (50%) R
PSI-PSSM: 1 (6%) Q
Multiple Alignment: 62/74 R
Multiple Alingment: 0/74 Q

R261Q

Figure 3. Histogram of PSI-Blast PSSM conservation scores for position 261

Substitution Scores:
BLOSUM62: 1
PAM1: 9
PAM250: 5
PSI-PSSM: 6 R
PSI-PSSM: 0 Q
Multiple Alignment: 1/74 R
Multiple Alignment: 0/74 Q

T266A

Figure 3. Histogram of PSI-Blast PSSM conservation scores for position 266

Substitution Scores:
BLOSUM62: 0
PAM1: 32
PAM250: 11
PSI-PSSM: 5 (40%) T
PSI-PSSM: 4 (40%) A
Multiple Alignment: 48/74 T
Multiple Alingment: 0/74 A

P275S

Figure 3. Histogram of PSI-Blast PSSM conservation scores for position 275

Substitution Scores:
BLOSUM62: -1
PAM1: 17
PAM250: 9
PSI-PSSM: 5 (29%) P
PSI-PSSM: -3 (0%) S
Multiple Alignment: 48/74 P
Multiple Alingment: 0/74 S

T278N

Figure 3. Histogram of PSI-Blast PSSM conservation scores for position 278

Substitution Scores:
BLOSUM62: 0
PAM1: 9
PAM250: 4
PSI-PSSM: 4 (33%) T
PSI-PSSM: -1 (2%) N
Multiple Alignment: 34/74 T
Multiple Alingment: 0/74 N

P281L

Figure 3. Histogram of PSI-Blast PSSM conservation scores for position 281


Substitution Scores:
BLOSUM62: -3
PAM1: 3
PAM250: 5
PSI-PSSM: 8 (84%) P
PSI-PSSM: -5 (0%) L
Multiple Alignment: 48/74 P
Multiple Alingment: 0/74 L

G312D

Figure 3. Histogram of PSI-Blast PSSM conservation scores for position 312

Substitution Scores:
BLOSUM62: -1
PAM1: 6
PAM250: 11
PSI-PSSM: 3 G
PSI-PSSM: -1 D
Multiple Alignment: 1/74 G
Multiple Alignment: 0/74 D

R408W

Figure 3. Histogram of PSI-Blast PSSM conservation scores for position 408

Substitution Scores:
BLOSUM62: -3
PAM1: 2
PAM250: 2
PSI-PSSM: 6 R
PSI-PSSM: -5 W
Multiple Alignment: 1/74 R
Multiple Alignment: 0/74 W

Mutations and secondary structure

Predicted secondary structure

We took the secondary structure prediction from Task 3:

Reference MSTAVLENPGLGRKLSDFGQETSYIEDNCNQNGAISLIFSLKEEVGALAK
DSSP --------------------------------------------------
Reference VLRLFEENDVNLTHIESRPSRLKKDEYEFFTHLDKRSLPALTNIIKILRH
DSSP --------------------------------------------------
Reference DIGATVHELSRDKKKDTVPWFPRTIQELDRFANQILSYGAELDADHPGFK
DSSP -----------------.....SBGGGGGGTT.S.------..TTSTTTT
Reference DPVYRARRKQFADIAYNYRHGQPIPRVEYMEEEKKTWGTVFKTLKSLYKT
DSSP .HHHHHHHHHHHHHHHH..TTS........HHHHHHHHHHHHHHHHHHHH
Reference HACYEYNHIFPLLEKYCGFHEDNIPQLEDVSQFLQTCTGFRLRPVAGLLS
DSSP HB.HHHHHHHHHHHHHS..BTTB...HHHHHHHHHHHT..EEEE.SS...
Reference SRDFLGGLAFRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFA
DSSP HHHHHHHHTTTEEEE......TT.TT..SS..HHHHHTTTTTTTTSHHHH
Reference QFSQEIGLASLGAPDEYIEKLATIYWFTVEFGLCKQGDSIKAYGAGLLSS
DSSP HHHHHHHHHHTT..HHHHHHHHHHHHTTTTT.EEEETTEEEE..HHHHT.
Reference FGELQYCLSEKPKLLPLELEKTAIQNYTVTEFQPLYYVAESFNDAKEKVR
DSSP HHHHHHTTSSSS..EE..HHHHTT....SSS..S..EEES.HHHHHHHHH
Reference NFAATIPRPFSVRYDPYTQRIEVLDNTQQLKILADSINSEIGILCSALQK
DSSP HHHHTS..SSEEEEETTTTEEEEE.HHHHHHHHHHHHHHHHHHHHHHHHH
Reference IK
DSSP T.


I65T

Not covered by the structure used for DSSP.

R71H

Not covered by the structure used for DSSP.

R158Q

The mutation affects a helix.

R261Q

The mutation affects a turn.

T266A

The mutation affect an unstructured region.

P275S

The mutation affects a turn.

T278N

The mutation affects an unstructured region.

P281L

The mutation affects an unstructured region.

G312D

The mutation affects a turn.

R408W

The mutation affects an unstructured region.

Predicting the effect of mutations with SNAP, SIFT and Polyphen2

SNAP

Execution

snapfun -i reference.fasta -m mutations.txt -o snap.txt

Result

mutation effect Reliability Expected Accuracy
R408W Non-neutral 4 82%
I65T Non-neutral 5 87%
R261Q Non-neutral 5 87%
G312D Non-neutral 1 63%
R71H Neutral 0 53%
P281L Non-neutral 3 78%
R158Q Non-neutral 6 93%
P275S Non-neutral 2 70%
T266A Non-neutral 2 70%
T278N Non-neutral 4 82%

SIFT

Execution

To run our predictions with SIFT we used the webservice. We had the following input (See also figure):

SIFT input
  • Sequence: Fasta sequence from the Uniprot entry P00439.
  • Substitutions: our ten selected substitutions
  • Database to search: UniRef90_2011_Apr
  • Median conservation of sequences: 3.00
  • Removed sequences: If sequence identity is greater than 90%

Results

Position Reference AA Mutated AA Predicted effect Score Median sequence conservation Sequences represented at this position
65 I T AFFECT PROTEIN FUNCTION 0 3.03 64
71 R H AFFECT PROTEIN FUNCTION 0.05 3.03 64
158 R Q AFFECT PROTEIN FUNCTION 0 3 64
261 R Q AFFECT PROTEIN FUNCTION 0 3.01 65
266 T A AFFECT PROTEIN FUNCTION 0 3.01 65
275 P S AFFECT PROTEIN FUNCTION 0 3.01 65
278 T N AFFECT PROTEIN FUNCTION 0 3.01 65
281 P L AFFECT PROTEIN FUNCTION 0 3.01 65
312 G D AFFECT PROTEIN FUNCTION 0 3.01 65
408 R W AFFECT PROTEIN FUNCTION 0 3 64

Polyphen2

Execution

To run our predictions with Polyphen2 we used the webservice. We had the following input (See also figure):

Polyphen2 input
  • Sequence: Fasta sequence from the Uniprot entry P00439.
  • Substitutions: our ten selected substitutions
  • Classifier model: HumDiv
  • Genome assembly: GRCh37/hg19
  • Transcripts: canonical
  • Annotations: missense

Results

#o_snp_id snp_id acc pos aa1 aa2 prediction pph2_prob pph2_FPR ph2_TPR
P00439_I65T P00439_I65T P00439 65 I T probably damaging 1 0.0001 0.0002
P00439_R71H P00439_R71H P00439 71 R H possibly damaging 0.936 0.0539 0.796
P00439_R158Q P00439_R158Q P00439 158 R Q probably damaging 1 0.0001 0.0002
P00439_R261Q rs5030849 P00439 261 R Q probably damaging 1 0.0001 0.0002
P00439_T266A P00439_T266A P00439 266 T A probably damaging 1 0.0001 0.0002
P00439_P275S P00439_P275S P00439 275 P S probably damaging 1 0.0001 0.0002
P00439_T278N P00439_T278N P00439 278 T N probably damaging 0.998 0.0114 0.269
P00439_P281L P00439_P281L P00439 281 P L probably damaging 1 0.0001 0.0002
P00439_G312D P00439_G312D P00439 312 G D probably damaging 1 0.0001 0.0002
P00439_R408W P00439_R408W P00439 408 R W probably damaging 1 0.0001 0.0002

Discussion

Some mutations can cause severe malfunctions if they occur at the wrong place. Using only sequence based predictions probably fail to predict the effect of such a mutation. Such a mutation might seem to be non-harmful regarding only general substitution scores or physico-chemical properties.

Mutations in Detail

I65T

The mutation changes the residue from unpolar to polar. The region, where the residue is located, is presumably a disordered region. Therefore it probably folds with the right binding partner. Even in PAM1 this mutation seems to take place quite often. Therefore theres seem to be some proteins, where this kind of mutation is allowed. In the PSSM of PSI-BLAST the mutated residue is not recorded in any of the sequences. The secondary structure of this residue could not be determined by DSSP, because the used structure does not contain it. SNAP predicts the mutation to be damaging with high reliability and accuracy. SIFT and Polyphen2 agree with this prediction.

Depending on the fold of the region, where the mutated residue is located, the mutation can cause severe results during the folding and therefore the binding properties of the disordered region. Therefore we would predict it to be probably damaging to the function of the protein.

R71H

The residues differ in their physiko-chemical properties. H has an aromatic group and it is basic. The residue is probably at the border of a disordered region. The general substitution matrices differ in their scoring. In the PAM matrices this substitution is quite okay. In BLOSUM62 it is disfavored. SIFT predicts the mutation to be damaging, but the score is in the twilight-zone. Polyphen predicts it to be damaging. SNAP predicts the mutation to be neutral, but with low reliability and average accuracy.

Since the residue is probably at the border of a disordered region. It's impact on the structure is perhaps not strong.

R158Q

R261Q

The mutated residue Q differs to R in the loss of the positive charge. Both residues are structurally very similar. The residue is part of a PFAM domain. Pymol was able to find a rotamer for the shorter residue Q, which fits almost perfectly the native rotamer of R. This change seems to be supported by the general substitution matrices. DSSP predicts the residue to be part of a turn. Therefore the positive charge of R is probably essential to establish the bonds, which are necessary for the turn. Directly after the residue starts a sheet. That means small changes can influence the sheet and therefore the protein structure and its function.

SNAP predicts the mutation to be harmful with high accuracy and reliability. SIFT and Polyphen2 agree to this prediction.

T266A

P275S

T278N

P281L

G312D

This mutation changes the physico-chemical properties of the acid in a quite drastic way. G is mutated to the polar, negatively charged and acidic residue D. At the wrong position in the structure this can cause quite some trouble. In the structure superposition both residues seem to occupy quite the same volume. The general substitution matrices differ in the scoring for this substitution. In BLOSUM62 this exchange seems to be slightly unfavored. In both PAM matrices the substitution is okay. DSSP predicts the residue to be part of a turn. Compared to G D does not loose any properties, which could be essential for the stabilization of the turn. The structure is perhaps not influenced.

SNAP predicts the mutation to be non-neutral, but the program is as unsure as we are with respect to the reliability score and the accuracy. SIFT and Polyphen2 predict it to be harmful without doubts.

If there is an influence of G312D then we would predict that its influence on the protein function is not that strong. Perhaps it does not even cause a symptom.

R408W

The physico-chemical properties of the wildtype and mutated residue are quite different. The mutation is aromatic and not positively charged. The position 408 is part of a PFAM domain, which means that this region is quite compact. Therefore even little changes can cause quite some trouble. In the superposition of the two residues, one can see that they differ quite strongly in their structures. Pymol was unable to find a more overlapping rotamer for the mutated W with the wildtype R rotamer. The scores in the substitution matrices support the assumption, that such a change is not very likely. DSSP predicts the residue to be unstructured. But there is a helix to the left and a sheet to the right. Small changes might influence these two structures and cause trouble in the protein function.

SNAP, SIFT and Polyphen2 agree with our observations. The mutation very likely harmful.

Complete Results