ADL: AutoDock Vina: New Question(s)

L. Michel Espinoza-Fonseca mef at ddt.biochem.umn.edu
Mon Apr 13 14:19:56 PDT 2009


Dear Warren,

> Dear Friends,
> I have been using Autodock Vina for the past 2 months (in fact I bypassed Autodock 4.0 and picked up my docking tools of trade >from the excellent Vina tutorial).  Recently, I blind-docked a drug-ligand onto a receptor protein using the latest Autodock Vina >1.0 beta 04.  It's sure fast!  I obtain a reasonable number, - 6.3 kcal/mol for the binding affinity of the ligand.  I wanted to calculate >the total energy of the docked protein, so I turned to ADT and used the command 'Compute Potential Using APBS', which is >under the menu command 'Compute' and then select 'Electrostatics'.  I got a value of 4.4716E4 kJ/mol.  I repeated the same >calculation on the protein without the docked ligand and I got 4.4525E4 kJ/mol for the potential.  Since I am new to ADT, I would >like you advice/comment regarding the following:

This procedure will help you if want to calculate *only* the
electrostatic contribution to enthalpy, as
Eelec=Ecomplex-Eprotein-Eligand, where each term corresponds to the
total electrostatic energy, and the electrostatic energy of the
complex, the protein and the ligand, respectively. You should keep in
mind that the electrostatic term often gets canceled by a desolvation
term, so even very large numbers in the electrostatic energy cannot be
realistically compared with the free energy of binding.

> (i) the numbers imply that overall the docked protein is unstable by about 200 kJ/mol relative to the undocked protein.  Therefore, >even though the ligand binds favorable to the active site on the protein (thus locally stabilizing the active site), overall the docking >destabilizes the protein, which in turn responds by sending the next signal.

Remember that what you obtain from the docking simulation is an
estimation of the *free energy*, which includes both enthalpic an
entropic terms, and not simply an estimation of the energy of the
system (that normally ignores solvation and entropic terms). Hence,
you should focus on the free energy rather than on the MM energy to
come up with a meaningful interpretation of your results.

I also think you're coming up with big conclusions, as you don't have
any dynamic evidence on what's actually happening with the protein
upon binding. The only thing you have is a static 3-D structure of
your complex and an estimated value of the free energy of binding.

> (ii) I am not an expert with ADT, so I was wondering if 'APBS' refers to some type of force field (AMBER, CHARM, etc).

APBS is a software package and not a force field.

http://apbs.sourceforge.net/

Cheers,
Michel

> Thanks!
> With Best Regards
> Warren
> Chicago, USA
>
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