Molecular Dynamics Simulations BCKDHA

Preparation

For the molecular dynamics simulation two mutations should be chosen. We decided to take one mutation, which leads to a drastic change in the amino acid properties and may therefore be crucial. The other mutation changes methionine to lysine, which have similar physiochemical properties and structures. The mutations we chose are the following:

• M82L: (in PDB position 37)
• C264W: (in PDB position 219)

Crystal water Extraction

repairPDB bckdha_mod.pdb -ssw 15 > crystalWater.pdb

bckdha_mod.pdb is the manipulated pdb from last tast, where the missing residues in the 1U5B pdb file were handled.

When trying to extract the crystal water we received an empty file, indicating that there is no crystal water below 15 Å in our pdb file.

Extract Protein

repairPDB bckdha_mod -nosol >wt.pdb

SCWRL

first, extract sequence from pdb file:

repairPDB bckdha_mod.pdb -seq > wt.seq

run SCWRL

scwrl -i wt.pdb -s wt.seq -o wt.pdb

wt.seq is the extracted protein sequence in all lower case letters. In the case of mutants the mutated residue is given in an upper case letter.

remove hydrogens

repairPDB wt.pdb -noh > wt.pdb

Concatenate protein and crystal water

As we didn't have crystal water, the concatenation step could be skipped.