AMBER Archive (2007)Subject: Re: AMBER: Potential of mean force, how to calculate rate of dissociation?
From: Catein Catherine (askamber23_at_hotmail.com)
Date: Fri May 04 2007  20:55:26 CDT
Dear All,
Thank you very much for your help.
Best regards,
Cat
>From: "David Mobley" <dmobley_at_gmail.com>
>ReplyTo: amber_at_scripps.edu
>To: amber_at_scripps.edu
>Subject: Re: AMBER: Potential of mean force, how to calculate rate of
>dissociation?
>Date: Fri, 4 May 2007 14:09:36 0700
>
>Thomas,
>
>>thanks for pointing this out David, I fully agree that what I said is only
>>true in the limit of full equilibration, which is hard enough to achieve
>>for a single bound ligand conformation and quite possibly impossible for
>>many dissociation processes. I guess one can sum it up that PMF's give you
>>an upper bound of the activation free energy that may be a very bad
>>estimate but should converge to the true one in the limit of infinite
>>sampling. Since the rate would depend exponentially on E(activation),
>>calculated rates would be even less reliable.
>
>Again, it depends on the reaction coordinate you pick. It's possible
>to pick a reaction coordinate such that you would never get the right
>activation energy regardless of how long you ran. I suppose if you
>simply pull radially, in the infinitesampling limit, you would
>eventually find the "most relevant" pathways out and average over
>those sufficiently. But in most applications radial pulling is
>probably more expensive than pulling in a particular direction with
>respect to the protein (since radial pulling involves sampling
>everywhere over a spherical shell at each r for convergence). And
>pulling in a specific direction, even in the infinitesampling limit,
>should just give you the activation barrier along that specific
>direction.
>
>But, as you note, it's true that these are an upper bound (assuming
>the force field is adequate) on the true activation barrier, so maybe
>they could still be useful.
>
>Best wishes,
>David
>
>
>>Regards,
>>
>>Thomas
>>
>>Dr. Thomas Steinbrecher
>>The Scripps Research Institute
>>10550 N. Torrey Pines Rd.
>>San Diego CA 92037, USA
>>
>>
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>
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