[gmx-users] Free Energy Topology between A and B.

[Nash, Anthony]

Dear all,

I¹m a total newbie when it comes to Thermodynamic Integration, and until
now I¹ve been happy with umbrella sampling. However, I¹ve found myself in
a situation where I believe TI would be the most appropriate technique.

I would like to determine the energetic contribution that a mutant amino
acid has to a protein-protein interaction. The structure is very complex,
so pulling along a reaction pathway is out of the question, thus an
alchemical path might work.

I wish to integrate from state A to state B. The number of atoms in the
wild type amino acid of state A are fewer that those in the mutant amino
acid of state B. The example given in section 5.7.4 of the manual
demonstrate integrating from propanol to pentane, but due to the GROMOS-96
FF each topology shares the same number of atoms. Atom PC2 and PC3 of
state A does not require redefining in typeB chargeB and massB, they are
transferred across as they are in both structures. How does one define a
mixed A B topology when the number of atoms differ? I.e., if those two
atoms in the above example were not needed in state B.

Thanks
Anthony