Re: [AMBER] Holding Host-Guest COM constant during binding enthalpy MD

From: Carlos Simmerling via AMBER <>
Date: Tue, 7 Nov 2023 18:49:50 -0500

I would try to get a stable complex before worrying about the enthalpy
part. It's hard to say why they dissociate without more detail. Do you have
periodic wrapping on? Maybe it's just an imaging problem then. Do you use
restraints to keep them together until the system is well relaxed? Might be
needed. What are the initial coordinates? If not from experiment, maybe it
isn't a good model. Do you know they actually should bind? If not you may
need to use restraints as above,but not turn off. A problem there is that
it might impact your enthalpy calculation.
If you do need restraints, I would guess the most reasonable would be some
sort of weak center of mass harmonic restraint. Which atoms to include
depend on what you know about the position of the guest in the host. These
restraints are fairly easy to set up, buy do depend on your system and how
reliable the initial coordinates are.

On Tue, Nov 7, 2023, 2:05 PM Meyer, Olivia (meyerok) via AMBER <> wrote:

> Good Afternoon,
> I have a general question regarding a host-guest system I am
> investigating. I am attempting to determine binding enthalpy using the
> method provided in the Computing Binding Enthalpies Tutorial, involving CB7
> and B2 as the respective host and guest. Although the general process of
> the tutorial is understandable, when I replicate this technique using a
> different host/guest system my guest and host are not staying bound (the
> earliest evidence of this is the NVT simulation, prior to any NPT
> simulations). The guest is leaving the host cavity, but I cannot calculate
> a binding energy if they are not bound. I have attempted to resolve this
> issue using multiple strategies, which I have listed below, where none of
> these strategies have provided the desired effect I am attempting to
> replicate.
> 1. Providing -ref coordinate files (this was just a guestimate-type
> solution)
> 2. Restraining the host and guest using 'RES 1 2' command with a
> restraining force of 100.0 (I have done this with ntc=2, ntf=2, ntr=0
> (scenario a—which does not keep the host-guest complex bound together),
> ntc=2, ntf=2, ntr=1 (scenario b—completely constrains their positions and
> does not allow any movement whatsoever)
> I am somewhat at a loss now, as I do not have anymore experience to move
> forward in an educated way, other than trying another method (potentially
> using the attach-pull-release method of the other binding enthalpy
> tutorial). If anyone has suggestions, I would be sincerely grateful.
> -Olivia
> Olivia K. Meyer
> Graduate Student, Kumari Lab
> University of Cincinnati
> James L. Winkle College of Pharmacy
> Department of Pharmaceutical Sciences
> 231 Albert Sabin Way, Cincinnati, OH USA 45229
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Received on Tue Nov 07 2023 - 16:00:03 PST
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