[gmx-users] Fwd: asking for help with dual-topology for TI

[Anton Feenstra]

Lei Zhou wrote:

> Dear gmx-users,
> 
> I am trying to set up a thermodynamic-integration to calculate the
> free energy difference between two ligands. Both of them contains over
> 30 atoms and are quite different from each other.  I am wondering
> whether GROMACS support dual-topology?  It is really a difficult job
> for a beginner to setup the topology file for TI, especially in the
> case of two very different ligands.

That's (partly) because it's a difficult subject.

> Can I just simply set all atoms in A to dummy atoms at lamda=1 and set
> all atoms of B to dummy atoms at lamda=0?

No - there are delicate statistical thermodynamical considerations that, 
basically, disallow that. It has to do with the fact that even these 
dummy atoms still represent degrees of freedom, and hence factor into 
the entropy. For some cases, it may be possible to correct for this, but 
I'm not the expert in this.

You may get good results by using a common intermediate (possible 
non-physical) reference state, e.g. like recently explored in the Van 
Gunsteren group.

-- 
Groetjes,

Anton

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|  _   _  ___,| K. Anton Feenstra                                     |
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