Task 8: MSUD - Molecular Dynamics Simulations

Task description

This week we are calculating a molecular dynamics (MD) simulation for two of our mutations and the wild type. For this we are using Gromacs and the AGroS script that mostly automates the process. As MD calculations take a lot of cpu time the script is run on the LRZ machines.

AGroS

The AGroS script runs through the following steps (taken from comment in the actual script):

1. Runs RepairPDB and findBreaks, additional scripts to adapt PDB files to MD reality.
2. Runs STRWater, an additional script that saves information for Structural Water Molecules in PDB file.
3. Runs SCWRL, a program employed to correctly assign side chain information to PDB structures.
4. Runs minimization in vacuum.
5. Creates water box, includes solvent (water with 0.1 [NaCl]) and neutralizes protein intrinsic charge.
6. Creates restrain files for each chain individually.
7. Runs solvent minimization with fixed Protein (backbone + side chains).
8. Runs minimization with fixed Backbone.
9. Runs short production NVT MD.
10. Runs short production NPT MD.
11. Runs Production MD.

In the first step AGrosS calls the clshwtr.pl script for our pdb structure which removes clashing water atoms from the structure. Interestingly after the the repairPDB script with the option '-nohoh' is started that removes all water atoms from the structure. After this the findBreaks.pl script checks for gaps in the pdb structue and aborts the run in case any are found.

The third step runs SCWRL to assign information about side chain placement to the pdb file. After this an energetic minimization in vacuum is calculated after which a waterbox with a size of 10A around the protein is created. The system is neutralized and ions for a 0.1 NaCl concentration are added.

In step seven and eight the protein is first minimized with a fixed backbone and side chains then only with a fixed backbone. Steps nine and ten run short simulations with fixed temperature (NVT) and fixed pressure (NPT) respectively. After all this finally the real MD simulation is run.

Mutations

A328T, Q125E, wt

Results

A328T

MD-simulation of BCKDHA_human with mutated residue A328T. Simulation was generated with AGros( Gromacs )