ADL: Theory in Vina tutorial video?

mcmartin at mcmartin at
Thu Apr 16 04:56:34 PDT 2009

Thank you Mark,

That was very helpful :) I just didn't see the co-relation between a
larger ensemble of conformations with a smaller decrease of entropy, but
your explanation was quite clear.

Thanks for also clarifying that AutoDock DOES take into account the
desolvation state of ligand and receptor, I guess its a new feature in
docking programs, since I read in a book (Essentials of computational
chemistry-. Cramer) that docking programs generally don't.

With kind regards,


> ----- Original Message -----
> From: mcmartin at
> Date: Thursday, April 16, 2009 3:33 am
> Subject: ADL: Theory in Vina tutorial video?
> To: autodock at
>> Hi all,
>> So I'm watching the vina tutorial video and I got a little puzzled
>> with the theory explanation. They say:
>> "It is often said that the global minimum corresponds to the native
>> conformation, however this is not correct, a deeper but narrower peak
>> may actually be less preferable, because of entropy"
>> Oleg says this while pointing at the conformation of lowest energy,
>> which as I have understood, is the "strongest" binding energy. There
>> are a couple of things in this sentence that I do not understand and I
>> hope
>> you can help me out:
>> 1. Why does he talk about a ligand-receptor complex with a "native"
>> conformation? I thought the term native conformation was strictly
>> applied to proteins with the proper functional folding?
> I think this is just intended to be a convenient shorthand for the "true"
> conformation that would, presumably, be observed
> in an NMR or crystal structure of the complex, if such was available.
> Native protein conformation is to biologically active
> protein structure as native ligand conformation is to the "active" ligand
> structure that's "competent" for binding.
>> 2. So I understand in the in silico experiment entropy is lost upon
>> ligand-receptor binding,  especially since AutoDock neglects the solvent
>> molecules (Unless the entropy of the desolvation state is taken into
>> account
>> with the AMBER force fields, which is not yet clear to me, even though
>> I have read Cornell et al. 1995) So why is a _wider_ peak more
>> preferable in terms of entropy? In other words, what does the width of
>> the peak
>> represent?
> Desolvation effects ARE modeled approximately in autodock's scoring
> function. I believe what Oleg is getting at is that, in
> addition to increasing entropy by displacing bound water, ligand binding
> is associated with a decrease in the
> conformational entropy of the ligand (and probably of the receptor as well
> in most cases). That is, the free ligand may
> readily take on many different low energy conformations whereas the range
> of bound conformations would be severely
> restricted by the requirement to maintain proper energetically favorable
> contacts with the receptor. A "narrow" peak in
> this context means one where the energy only stays low within some small
> region (in terms of the hypervolume defined by
> the ligand's state variables - translations, rotations, torsions) and then
> increases steeply with further changes in the
> ligand's state variables, thus limiting the size  of the conformational
> ensemble (in terms of hypervolume) that can fit near
> the energy minimum. A "wide" peak would have a larger low energy region
> (and possibly shallower gradients up the sides),
> which could accommodate a larger ensemble and, therefore, would be
> associated with a smaller decrease in
> conformational entropy. A smaller decrease in conformational entropy would
> mean, all other things being equal, a lower
> free energy of binding.
> Regards,
> Mark
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