[gmx-users] Protein Solvent Dynamics - Coordinates for docking

[Mark Abraham]

ram bio wrote:
> Dear Mark,
> 
> You mean that I should consider a configuration with the lowest total
> energy for docking studies..Please clarify and suggest me.

If you read your docking program's documentation, they are using their 
"energy" as a some kind of approximation to a free energy of ligand 
binding (or some such). There could be all kinds of ad-hoc contributions 
that they may have been able to demonstrate worked usefully enough on 
their test set to be worth including.

There's no reason to assume an MD potential "energy" (which itself is a 
combination of more-or-less ad-hoc parameters) would correlate with the 
above, since the MD potential wasn't parameterized to do that. It'd be 
especially flawed to suppose that the fact that energy in MD is 
distributed over PE and KE is immaterial. Low PE just means high KE.

To identify favourable ligand-binding orientations with MD requires an 
immense amount of sampling. In effect, you need to do enough MD to allow 
the ligand to come in and out of the site many times in many different 
ways and to compare the relative frequency so that you can also estimate 
the entropy component of the free energy change associated with various 
binding modes relative to each other. Even for implicit solvent 
calculation models, the history of computing probably doesn't provide 
enough cycles to do this with decent accuracy. Hence, docking.

MD can be useful in more limited "docking" studies - a highly 
unfavourable binding conformation will fly apart rapidly - but you'd 
hope the docking force field could tell you about those cases!

It sounds like you should really be doing some more background reading 
about docking and MD, to better understand the methods you're using.

Mark

> On Thu, Oct 22, 2009 at 3:56 AM, Mark Abraham <Mark.Abraham at anu.edu.au> wrote:
>> ram bio wrote:
>>> Dear Justin,
>>>
>>> Thanks for the suggestion and advice.
>>> As i have used a modelled protein and want to obtain the lowest energy
>>> configuration of the protein by doing dynamics,
>> That's all very well, but what will that give you other than a set where the
>> partition of total energy into potential and kinetic was skewed one way?
>>
>> Mark
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