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

From: Gert Kruger via AMBER <>
Date: Wed, 8 Nov 2023 05:44:15 +0000

Dear Olivia,

Are you using QM for the guest molecule and the atoms in the active site where it is binding?

I would imagine this will improve the binding interactions.

Can you share with us the host guest system you are using (even just a general description)?

If the host leaves the binding site, it is possible due to the chemical forces being weak. Seeing the system will help us to tell you if one expects good or weak binding.

Best wishes
Gert Kruger

On Tue, 2023-11-07 at 19:00 +0000, 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 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 - 22:00:02 PST
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