Re: [AMBER] Binding energy of ligand with homology model

From: Daniel Mermelstein <>
Date: Wed, 3 Jan 2018 13:31:50 -0800

Hi John,

So sorry for the delay, things got busy around the holidays and this
slipped through the cracks.

What is your ultimate goal here? Is it just to find the relative energies
of each of these conformers? If so then MMPBSA is a good choice. Another
option would be alchemical free energy (MBAR or TI), which will take
longer, and may require you to restrain your ligand to prevent it from
leaving the starting local minima and exploring alternate conformations.

I should clarify this is all assuming your binding site is not going to
change much.

Hope this helps,

Happy new year!


On Thu, Dec 21, 2017 at 11:45 AM, Morrow,John Kenneth <> wrote:

> Hello, I have a small molecule inhibitor of a protein-protein interaction,
> and AMBER simulations of the complex shows the ligand can undergo
> significant rotations and (almost 180 ° among 1 axis) and different
> conformers. The ligand is small and really only has 3 major functional
> groups<>. It is worth
> mentioning that this binding pocket is not complete, so the starting
> structure was built from a homology model.
> I would like to have some binding energy calculations of the ligand in
> these different conformations. I found this post discussing the different
> methods:
> But as this post is over 5
> years old, I would like to ask the community if there are any newer
> recommendations/thoughts. Simulation time is not a concern, but ease of use
> is, as I am a relatively novice AMBER user.
> Thank you,
> John
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Daniel J. Mermelstein, Ph.D candidate
McCammon & Walker Groups
Department of Chemistry & Biochemistry
University of California, San Diego
AMBER mailing list
Received on Wed Jan 03 2018 - 14:00:02 PST
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