[AMBER] SHAKE failed for hydrogens that interact with soft-core and/or no-SHAKE atoms

From: He, Amy via AMBER <amber.ambermd.org>
Date: Wed, 15 Feb 2023 22:17:14 +0000

Dear Amber experts,

I’m using sander.MPI in Amber 20 for dual-topology TI simulations with soft core potential. I am doing a single-step transformation of residue protonation states in my simulation. My system is composed of a protein in explicit waters.

I was able to calculate dG for a few types of transformations in my system and similar systems with my dual-top TI protocol. But there’s one HIP/GLU->HID/GLH transformation that kept failing.

In some windows, SHAKE failed for hydrogens in contact with soft-core or no-SHAKE atoms. The one or two hydrogens are typically the non-polar, non-solvent exposed hydrogens that interact with the soft-core atoms or the no-SHAKE residues. They are NOT in the same residue that goes through alchemical transformation.

My soft-core atoms are (if present):
HIP HE2 (disappearing), GLU OE2, GLH HE2 (appearing)

My No-SHAKE atoms are:
The two residues that go through alchemical transformations.

I have also tried different selections of No-SHAKE atoms. Then SHAKE failed for different hydrogens at the SHAKE/No-SHAKE interface. Maybe I should expand the No-SHAKE region a lot more. But the simulations would become quite expensive for me…

I wish to get some general suggestions from our community to resolve this issue --

What might be the cause of SHAKE failures, in the context of alchemical simulations with soft-core potential? Bad combinations of soft-core, SHAKE and no-SHAKE atoms?

Any comments/suggestions would be really appreciated.

Best regards,

Amy He
Chemistry Graduate Teaching Assistant
Hadad Research Group
Ohio State University
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Received on Wed Feb 15 2023 - 14:30:03 PST
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