Part 3: Mutating Proteins and MD Setup
In this part of the workshop you have seen how to set up a molecular dynamics simulation starting from a PDB file. You have seen how you can mutate residues in a protein, how to add hydrogens and missing atoms, how to solvate the biomolecules in a periodic box of water, and how to prepare a system for a dynamics simulation (minimisation, heating and NVT and NPT equilibration). You have also seen how molecular dynamics provides a computational microscope to zoom in to watch biomolecules moving at the atomic scale. In the case of H7N9 neuraminidase, you have seen how even a quick dynamics simulation reveals the change in binding mode of zanamivir when arginine 292 is mutated to lysine 292. As revealed in this paper, this change in binding mode is associated with a reduction in binding affinity of the drug.
If you would like to learn more about molecular dynamics, then the different MD programs come with excellent tutorials, e.g.
Molecular dynamics is just one of many different computational molecular modelling techniques available to help you model biomolecules. If you want to learn more about other methods you can follow these tutorials;
- Monte Carlo Methods for Biomodelling
- Mixed Quantum Mechanics / Molecular Mechanics (QM/MM) Modelling for Free Energy Simulations