First of all, thanks for your comments.
> You can use methods such as umbrella sampling [..] or metadynamics [..]
> (rather than relying on chance observations during your equilibrium MD
run).
Agreed. But I have never used those techniques myself and I am afraid of
ending up multiplying my problems rather than solving one of them. :) I
think maybe I could first experiment a bit with energy minimization
starting from a configuration close (but not equal) to cis. So far, I only
tried to experiment with high-temperature MD to encourage the transition.
> If the cis-form is really more stable
As a matter of fact, the trans isomer is the natural form, but
experimentally in aqueous solution it converts to (and remains) cis upon
aging of the sample, or by sunlight radiation.
> I don't know if GAFF or AMBER are particularly well setup to handle
accounting
> for the effects of pi-electrons (maybe someone can comment). [..]
> there may also be significant polarization effects that you aren't
> taking into account unless you use a polarizable forcefield.
I really hope that someone can comment on that, too. After all, this looks
to me a basic question of molecular modeling (such as "can classical MD
model this kind of system?").
> Having said all that, maybe it can still work but you just haven't derived
> the charges accurately. How did you get the partial charges, did you use
> the RESP server?
Indeed, optimization of charges was intended to be my following step. In
fact, at the moment I am using charges suggested by UCSF Chimera (AM1-BCC),
as they looked reasonable compared to those used in Amber99SB, e.g. in the
side-chain of a TYR residue. The next step should have been to use the RED
server, but any other suggestion is welcome.
Still, I have the sensation that this issue could affect the detailed
optimization of the final structure, but not prevent altogether the
possibility of reaching a cis (or quasi-cis) conformation.
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Received on Thu Oct 18 2012 - 11:30:07 PDT
