[AMBER] About polar solvation term in MMGBSA decomposition results

From: xiangyu via AMBER <amber.ambermd.org>
Date: Wed, 14 Jun 2023 09:57:56 +0800 (GMT+08:00)

Hello Amber Users,

I used mmgbsa to analyze the importance of each of binding residues in binding of a ligand to a protein. I have some issues understanding some of the results. The Delta polar solvation terms (complex –ligand-protein) of the residues participating in forming hydrogen bond/ionic bond with ligand is more positive than the Delta electrostatic term, indicating that when forming the complex, the increase change in solvation energy compensates the decrease of electrostatic change. Does it mean that forming hydrogen bond/ionic bond is in fact unfavorable in binding the ligand to protein? Apparently to me, this is counterintuitive, since from both crystals and MD results, those hydrogen bonds are very stable. And in a FEP test, if I remove the polar group of ligand that participate in the H-bond, the FEP become very positive. Also, I noticed that electrostatic energy terms of LYS and ARG no matter interacting with ligand or not are always positive while the polar solvation terms are always negative., And for GLU and ASP, it is opposite. I'm confused about this result. I used the same gb setup in tutorial (igb=5 saltcon=0.1)

  total van der waal electrostatic polar solvation nonpolar solvation GLU 231 -0.602 0.050 -1.295 0.031 -46.182 0.076 47.09 0.07 -0.21 0.001 TYR 223 -0.366 0.020 -0.421 0.023 -3.557 0.030 3.73 0.02 -0.12 0.001 PHE 226 -2.8406 0.0320 -2.8299 0.0270 -5.4634 0.0422 5.7657 0.0293 -0.3130 0.0017

Thanks in advance for any help

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Received on Tue Jun 13 2023 - 19:00:02 PDT
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