simtk.org

Hello all,

I am interested in using OpenMM to simulate protein systems with small molecule ligands present, using openff to parameterize the small molecule.

I see in the documentation protocol examples for creating a protein-ligand topology with interchange, but also directly using the openff toolkit to create parameters for the ligand separately. Given that there are a few tutorial/documentation pages that cover this subject with slightly different protocols/methods, I was hoping to get some feedback from more experienced users on what is the best practices for parameterizing a small molecule+protein system in explicit water.

For instance is my best bet to follow the protocol outlined in the toolkit showcase here which uses interchange: https://github.com/openforcefield/openf ... case.ipynb

Or this protocol which does not use interchange to parameterize the ligand and then to create the protein-ligand system using those parameters (in ambertools for example): https://github.com/openforcefield/openf ... rmed.ipynb

Do the parameters assigned to the small molecule vary depending on whether interchange is used?

I apologize if these questions have been addressed elsewhere I did try to search the forums for threads related to small molecules before posting. Thanks for your time and help!

--Steve

So far as I know, Interchange is a recently added class that just provides a different interface to the same parametrization code. For protein-ligand systems, the recommended approach is to use OpenMM's ForceField class for the protein, and add a SMIRNOFFTemplateGenerator for the ligand. See https://github.com/openmm/openmmforcefi ... parameters.

I suggest asking on the OpenFF Toolkit github. The developers can tell you if there are any differences in the results from the different approaches.

Thanks for the quick reply! Appreciate the help!