VMD-L Mailing List

From: Vermaas, Josh (vermaasj_at_msu.edu)
Date: Mon Feb 15 2021 - 13:51:56 CST

Hi Manas,

I think FEP in this case would be overkill, and not as straightforward as using the appropriate collective variable. http://www.ks.uiuc.edu/Training/Tutorials/science/umbrella/REUS-1D.pdf would be a good start, coupled to a hydrogen bond or distance or dihedral angle colvar that describes the salt bridge. You could also use ABF or other techniques to sample the same reaction coordinate as well, but in this case an alchemical treatment would probably be more painful.

-Josh

On 2/15/21 2:02 PM, Manas Kohli wrote:
Dear Peter,

Thank you for your response. If I were to do free energy calculations, how would I go about doing them for intramolecular salt-bridges i.e. between two amino acids in the same transmembrane protein? So far I got links for looking at binding free energy between a ligand and protein but I don't think that's what I'm after. Any help would be really appreciated.

Thanks and Best Regards,
Manas

On Mon, Feb 15, 2021 at 5:07 PM Peter Freddolino <petefred_at_umich.edu<mailto:petefred_at_umich.edu>> wrote:
Hi Manas,
I think it is really important for us to know what your end goal is for this calculation. What energy are you really looking for? NAMDenergy is giving you the actual nonbonded energy (Coulomb + LJ) of the interacting groups in the force field of your calculation. If you're looking for something like the contribution of a salt bridge to the stability of a particular confirmation, or inter-molecular complex, you need to be getting into the world of free energy calculations. This is beyond what namdenergy provides. Just coming up with an ad hoc dielectric constant is unlikely to help the situation.
Best,
Peter

On Mon, Feb 15, 2021 at 10:38 AM Manas Kohli <manaskohli1_at_gmail.com<mailto:manaskohli1_at_gmail.com>> wrote:
Dear Daniel,

Thank you for your email! I realised that the interaction energy is indeed what I was after and after some more reading I realised I needed to adjust the dielectric constant to get a more physiologically representative result. My salt-bridge exists at the extracellular face of the protein i.e. it faces water. Would you know of an appropriate dielectric constant to use for this calculation? Thank you in advance!

Best wishes,
Manas

On Mon, Feb 15, 2021 at 1:23 AM Daniel Fellner <dfel694_at_aucklanduni.ac.nz<mailto:dfel694_at_aucklanduni.ac.nz>> wrote:
That seems about right, what's the issue?

Daniel Fellner BSc(Hons)
PhD Candidate
School of Chemical Sciences
University of Auckland
Ph +64211605326

On Mon, Feb 15, 2021 at 2:56 AM Manas Kohli <manaskohli1_at_gmail.com<mailto:manaskohli1_at_gmail.com>> wrote:
Hi all,

I'm trying to calculate the free energy between two residues in a salt-bridge in my protein structure. I used the NAMD energy plugin and for input I specified protein and resid x and similarly protein and resid y for the two residues to select for. According to the NAMD energy documentation, the output should be in kcal/mol but I seem to be getting values in the range -100kcal/mol for an individual salt-bridge energy calculation. Am I doing something wrong in the calculation phase or specifying the wrong input? I know it may be difficult to troubleshoot the problem without seeing the structure but if anyone has a general idea, I'd appreciate it and can attach sample pdbs and similar information in subsequent emails if that helps.

Thanks and Best Regards,
Manas 

--
Josh Vermaas
Assistant Professor, MSU-DOE Plant Research Lab and Department of Biochemisty and Molecular Biology
vermaasj_at_msu.edu<mailto:vermaasj_at_msu.edu>
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