Alchemy Support for Virtual Sites

[bieniekmateusz]

Hi,

I am working on absolute hydration free energies in molecules that contain virtual sites and I am using alchemy.py.

It appears that the virtual sites are treated the same way all other particles are. I removed the exception in AbsoluteAlchemicalFactory to test it.

In the simplest case of hydration free energies, when annihilating electrostatics and decoupling sterics, it appears that virtual sites are scaled appropriately. For example, pyridine with a virtual site has the absolute solvation free energy -4.399 kcal/mol, with the mirrored system in gromacs outputting -4.47 (0.02) kcal/mol. Pyridine without a virtual site gives -1.225 and in gromacs it is -1.15 (0.02). Based on similar tests it seems that the virtual sites are treated correctly.

So, could you elaborate why the systems with virtual sites are blocked in alchemy.py? Is it in case the user tries to annihilate the sterics (ie unpredictable positions), or are there known issues that have to be handled separately?

Many thanks, Mat

Code example for the disappearing of a molecule: solution leg. https://gist.github.com/bieniekmateusz/ecfb97000d8985f3132d75acf37dd2c5