Thank you Jason,
Just a clarification.
I quote your message:
>> 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.
Do you mean single or three-trajectory processing?
Thank you once again
George
> On 24 Aug 2015, at 20:02, Jason Swails <jason.swails.gmail.com> wrote:
>
> On Mon, Aug 24, 2015 at 12:29 PM, George Tzotzos <gtzotzos.me.com <mailto:gtzotzos.me.com>> 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
> states).
>
> 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
> effects.
>
>
>> 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.
>
> HTH,
> Jason
>
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
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Received on Mon Aug 24 2015 - 12:30:03 PDT
