Re: [AMBER] binding energy of multiple ligand-receptor complex

From: Jason Swails <>
Date: Fri, 4 Dec 2009 15:20:58 -0500

If you don't know the order of the ligand binding, then you'd probably have
to do all permutations of the ligand binding order, like Dr. Steinbrecher

However, I can imagine that binding order is often associated with
conformational changes which would not be captured by MM/PBSA applied to a
single trajectory. You may have to do multiple MD simulations with various
ligands bound to get enough sampling of the intermediate complexes to get a
reasonable result. MM/PBSA will only give you information about the order
of complementary binding if the effect of the second ligand binding by the
presence of the first ligand is purely electrostatic (or VDW).

Good luck!

On Fri, Dec 4, 2009 at 4:47 AM, <> wrote:

> Hi all,
> >> Now I am running MD simulation for multiple ligand-receptor complex
> >> (such as 3-4 ligand bind 1 receptor to form one complex) and want to
> >> calculate the binding energy. If it is single ligand - single receptor
> [...]
> > you can do several MM-PBSA calculations then.
> > When you have a receptor with two ligands:
> > Define calculation1 with ligand1 and receptor1 where ligand2 is part of
> > the receptor.
> > Then define calculation2 with ligand2 and receptor2 where ligand1 is part
> > of the receptor.
> Wouldnt that double-count the ligand-ligand interaction? I my opinion, you
> would have to pick a sequence in which the ligands bind and then do MMPBSA
> for R + L1, then R-L1 + L2, R-L1-L2 + L3 and so on. Additionally, if you
> permute the sequence, you will get some info about (anti-)cooperativity of
> binding and maybe an idea of the real order in which ligands bind...
> Kind regards,
> Dr. Thomas Steinbrecher
> BioMaps Institute
> Rutgers University
> 610 Taylor Rd.
> Piscataway, NJ 08854
> _______________________________________________
> AMBER mailing list

Jason M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Graduate Student
AMBER mailing list
Received on Fri Dec 04 2009 - 12:30:03 PST
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