[gmx-users] FEP in sugar

[K.A. Feenstra]

hugo verli wrote:
> 
[...]
> 
> Could these problems be dued to dificulties of the gmx forcefield in simulate
> sugars? The topology for the sugar was generated with prodrg.
> Or these problems can arise from the strong intramolecular interactions?
> Is there any way to overcome these problems? I can make the two transformations
> only changing the topology lines and runing a new dynamics. But doing so I will
> neglet the energy information about the transformation.

First off, if you're using a PRODRG topology, it is (by definition) not 
parameterized for your particular molecule and system. Thus, you should 
be careful to expect 'unrealistic' behavior from your molecule and check 
the results carefully (as you seem to be doing!). But, the PRODRG topology
*will* be a very good starting point, and saves you a lot of manual labor!

I've seen many of the previous mails on this discussion and have 
wondered how FEP would in any case be able to promote the dihedral
transition from chair to boat (c-b) or vice versa (b-c), since 
these states do not involve a change in topology and/or parameters.
Or, you could add 'artificial' parameters which would force the
molecule to adopt the one or the other conformation. Also, what
I could think of as an option, is to do free energy integration,
where the integration goes along the conformational pathway from
the one to the other conformation, keeping only the appropriate
dihedrals constrained (e.g. by transforming them to impropers and
setting the desired angle parameter). If I'm correct this will
give you the free energy profile of the pathway.

I'm not a sugar chemist, but if I recall, b-c or c-b transitions
will occurr frequently. It must be known at which rate they normally
occur, which will tell you whether you should expect to see a transition
in the time frame of your simulation. If you should expect it, but don't
see it, your parameters are wrong. Otherwise, if you can't expect to
see the transition(s), you should expect to end up or stay in the most 
stable one, which in your case seems to be the boat.

> Many thanks in advance and apologize for the insistence.

The most stupid question is the one you didn't ask... ;-)


-- 
Groetjes,

Anton
 ________ ___________________________________________________________
|        | Anton Feenstra                                            |
| .      | Dept. of Pharmacochemistry - Vrije Universiteit Amsterdam |
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