Re: [AMBER] working with mmpbsa with protein and three ligands in same complex

From: David A Case <>
Date: Sun, 17 Jan 2021 10:16:54 -0500

On Sun, Jan 17, 2021, Sadaf Rani wrote:

>I have a query and need your suggestions, please. I want to calculate
>ligand binding affinities of a protein-ligand complex in which I have 1
>ligand and two cofacors in the same complex. How should I calculate binding
>affinities of all with protein using mmpbsa? Do I need to built separate
>complexes for all of the three ligands (ligand plus cofactors)?

Don't be confused by the terms "protein", "ligand" and "complex". MMPBSA
doesn't know any chemistry, it effectively always treats a two-component
system, A + B -> C, where A, B and C can be anything you want.

To describe the binding of three components, you could do some combination
of the following calculations, depending on what information you wish to
obtain; (in this table, "C" would alway be the combination of "A" and "B"):

               "A" "B"
1. protein ligand
2. protein+ligand cofactor1
3. protein+ligand+cofactor1 cofactor2
4. protein+cofactor1 ligand

....etc...etc. The order of the calculations doesn't matter, at least
in principle. And you probably don't need all the steps. With a protein
plus three binders, there are *many* possible states, depending on whether
each binder has its own pocket (and so can only bind in one place), and
whether the two cofactors are the same or different. If each binder can
only bind in its "own" pocket, you would have

       nothing bound 1 state
       1 item bound 3 states
       2 items bound 3 states
       3 items bound 1 state

But is is very rare that you would want to simulate all of them.

...hope this helps....dac

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Received on Sun Jan 17 2021 - 07:30:02 PST
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