YANK Support for Multiple Conformational States

[mmahmedgithub]

Hi,

I am working on applying ABFE simulations for a bunch of ligands-target pairs. I am wondering if YANK supports multiple conformational states to enhance the statistical sampling of the apo (completely decoupled) state of the protein/receptor. My protein undergoes significant conformational changes in the apo form, transitioning between different microstates with high energy barriers. It seems that the sampling algorithms in YANK struggle to address this issue effectively within a practical timeframe for ABFE applications.

Do you have any suggestions? I am aware of some successful studies in this area but am unsure of tractable solutions within YANK/OpenMM.

Thanks,
Marawan