Molecular Dynamics Simulations Analysis Gaucher Disease

A brief check of results

We briefly checked the length of the MD simulations via gmxcheck:

gmxcheck -f traj.xtc 

Since we used the AGroS paramter -lengthMD 10, we expected the MD simulation to be 10ns long. gmxcheck reported for each simulation 2001 frames and a time step of 5ps per frame which amounts to the expected length of 2001*5ps=10ns.

We further investigated the runtime of the MD simulation by looking at the log files. The simulation of the WT took approximately twice as long as the other two mutations since we used only 16 instead of 32 cores. Performing a MD simulation over 1s would take more than 100000 years if the same hardware were used than we did.

<figtable id="tab:runtime">

Name	Runtime	ns/day	years/1s
WT	16h25:59	14.605	187536
L470P	9h20:49	25.677	106699
W209R	9h18:47	25.770	106314

Runtime of the MD simulations and the estimated runtime for a simulation length of 1s. </figtable> The computation of the energy term Coul(T) + LJ [W3-W3] accounted for most (47%) of the floating point operations.

Visualization

</figure> </figure> </figure>

Wildtype

L470P

W209R

Visualization of the MD simulations. Red: the active site residues E235 and E340; Blue: the mutated residue.

<figure id="fig:gif_wt">

<figure id="fig:gif_L470P">

<figure id="fig:gif_W209R">

Quality assurance

</figure> </figure> </figure>

Wildtype (1.0069/-0.0423231)

L470P (0.996977/0.0144563)

W209R (1.00887/0.00535799)

Development of the pressure during the MD simulation. In brackets: average/total-drift.

<figure id="fig:qual_pres_wt">

<figure id="fig:qual_pres_L470P">

<figure id="fig:qual_pres_W209R">

</figure> </figure> </figure>

Wildtype (297.912/0.00443415)

L470P (297.907/-0.00147577)

W209R (297.915/0.0095005)

Development of the temperature during the MD simulation. In brackets: average/total-drift.

<figure id="fig:qual_temp_wt">

<figure id="fig:qual_temp_L470P">

<figure id="fig:qual_temp_W209R">

</figure> </figure> </figure>

Wildtype (-939801/-450.018)

L470P (-940007/-705.14)

W209R (-940568/-355.406)

Development of the potential energy during the MD simulation. In brackets: average/total-drift.

<figure id="fig:qual_pot_wt">

<figure id="fig:qual_pot_L470P">

<figure id="fig:qual_pot_W209R">

</figure> </figure> </figure>

Wildtype (-768901/-447.47)

L470P (-769094/-705.985)

W209R (-769675/-349.952)

Development of the total energy during the MD simulation. In brackets: average/total-drift.

<figure id="fig:qual_tot_wt">

<figure id="fig:qual_tot_L470P">

<figure id="fig:qual_tot_W209R">

</figure> </figure> </figure>

Wildtype (6860: 2.72/3820: 2.08)

L470P (365: 2.28 / 7395: 2.08)

W209R (9720: 2.61 / 9180: 1.95)

Minimal distance to the adjacent cell with respect C-alpha atoms (black) and all protein atoms (red). In brackets: time frame and minimal distance for c-alpha/protein atoms.

<figure id="fig:mindist_wt">

<figure id="fig:mindist_tot_L470P">

<figure id="fig:mindist_tot_W209R">

RMSF

</figure> </figure> </figure>

Wildtype

L470P

W209R

MD simulations with residues colored by the g_rsmf B-factor (rainbow). Sticks: residues with a B-factor > 120. Purple: the mutated residue.

<figure id="fig:rsmf_wt"> File:Rsmf wt.png

<figure id="fig:rsmf_L470P"> File:Rsmf L470P.png

<figure id="fig:rsmf_W209R"> File:Rsmf W209R.png

</figure> </figure> </figure>

Wildtype

L470P

W209R

RMSF per residue with respect to the C-alpha atom.

<figure id="fig:rsmf_c_wt">

<figure id="fig:rsmf_c_L470P">

<figure id="fig:rsmf_c_W209R">

</figure> </figure> </figure>

Wildtype

L470P

W209R

RMSF per residue with respect to all atoms.

<figure id="fig:rsmf_p_wt">

<figure id="fig:rsmf_p_L470P">

<figure id="fig:rsmf_p_W209R">