[gmx-users] free energy calculation on amino acid mutation

hannes.loeffler at stfc.ac.uk hannes.loeffler at stfc.ac.uk
Thu May 26 19:35:23 CEST 2016

That really depends on how you approach the problem.

When you choose a dual topology approach you would need to decide where to branch off but basically end up with duplicating parts of the residue.  Sounds like that's what you were trying to do.

In the single topology approach you would match as many atoms as possible and balance just the missing atoms with dummies (as opposed to the dual approach where you may have lots of them).  As the bonded network stays the same you would not need to make any modifications to those.  I do not see any reason why you would not want to use this approach in your specific case (LEU->GLY).

There is a tool out there that you should probably give a try: pmx.  I believe it uses the single topology approach.

From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se [gromacs.org_gmx-users-bounces at maillist.sys.kth.se] on behalf of Yi An [anyiphysics at gmail.com]
Sent: 26 May 2016 17:44
To: gromacs.org_gmx-users at maillist.sys.kth.se
Subject: [gmx-users] free energy calculation on amino acid mutation

Hi Gromacs users,

I'm trying to calculate the relative binding free energy of a certain
ligand when a leucine in the ligand binding site is mutated to glycine. The
concept is simple but I have met some difficulties creating topology files
for free energy calculation. I have two questions I wish you guys can help:

1. Let's say my protein have 200 residues and the leucine I want to mutate
is in the middle (80 for example). When I tried to edit the topology of
this protein, I found that since the number of atoms changed, I need to
make lots of changes for bond, angle, and dihedral parameters. Is my
feeling correct?

2. If my understanding is correct, I wish there are some existing scripts
which can help people create topology file for mutational free energy
calculation. I will highly appreciate if you guys tell me where I can find

Thank you very much.

Yi An
Postdoctoral Research Associate
UNC-Chapel Hill
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