Hello,
On Thu, Aug 19, 2010 at 12:32 AM, Catein Catherine
<askamber23.hotmail.com>wrote:
>
> Dear Sir/Madam,
>
>
>
> I am using PMF to study a drug dissociation pathway.
>
>
>
> I did ~ 3ns for each window.
>
>
>
> I found the dissociation pathways seems to be reasonable. However, the
> activation energy was as high as 300 kcal/mol.
>
>
>
> Could you mind to share your experience with me on if the activation energy
> of as high as 300 kcal/mol seems reasonable when a conformational change in
> the protein receptor is needed to dissociate a drug?
>
If it's a large conformational change, then it is likely that 3ns is pulling
too fast to regularly sample near-equilibrium (reversible) pathways (i.e.
the biassing potential will do too much work since the process will be
HIGHLY irreversible). How far are you pulling over these 3 ns? Can you
slow the pulling down significantly to see if this reduces the activation
barrier?
Good luck!
Jason
>
>
> If it is not an reasonable, would you kindly suggest the protential source
> of error of this analysis?
>
>
>
> Best regards,
>
>
>
> Catherine
>
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>
--
Jason M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Graduate Student
352-392-4032
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Received on Wed Aug 18 2010 - 23:30:05 PDT
