Re: [AMBER] Solvent accessible surface area (SASA) calculation in CPPTRJ

From: Jason Swails <>
Date: Mon, 24 Aug 2015 13:02:33 -0400

On Mon, Aug 24, 2015 at 12:29 PM, George Tzotzos <> wrote:

> I’m jumping in this one as I have a similar situation.
> Following the suggested procedure (i.e. "A + B - (AB) will give you the
> buried area”) for:
> 1. dimer (no ligands) and
> 2. dimer plus ligands
> and assuming that 2 > 1, would it be legitimate to assume that the
> difference in buried area is due to the ligands?

​Assuming you're using a single-trajectory approach (where bound and
unbound conformations are identical), I think yes. But in this case, you
can take it even further -- even if 2 < 1, the difference comes from the
ligand "burying" previously-exposed residues. Otherwise, no (since you
wouldn't have a frame-by-frame comparison of bound and unbound SASAs since
the same *exact* conformation never appears in both the bound and unbound

If you're talking about an average over a long trajectory, the differences
could come from either allostery ​​or differences from the ligand
directly. You would need to do more analyses to disentangle the two

> In the affirmative is there a way to validate this?
​In the single-trajectory processing (where you get a frame-by-frame
difference between bound and unbound SASAs), there's no other explanation
for a difference in SASA, so the ligand *must* be the culprit.

In the latter case, the difference also *must* be from the ligands,
assuming you have converged ensembles in both the bound and unbound states
(this is a big *if*). But the effect could be indirect, as through
allostery, or direct in how it modifies the solvent accessible surface near
the binding site. If you want to argue that it's a direct effect, you
would need to have some way of quantifying the allosteric effects with
error bars smaller than the actual difference in the SASA. For a large
system, this can be very difficult to do.


Jason M. Swails
Rutgers University
Postdoctoral Researcher
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Received on Mon Aug 24 2015 - 10:30:03 PDT
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