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choderalab / yank

An open, extensible Python framework for GPU-accelerated alchemical free energy calculations.
http://getyank.org
MIT License
174 stars 69 forks source link

Is it possible to use enhanced sampling algorithms such as REST/REST2? #1277

Open jackzzs opened 2 years ago

jackzzs commented 2 years ago

In commercial software such as Schrödinger's FEP+, FEP is accelerated by enhanced sampling methods such as REST2, is it possible to achieve a similar function in yank? In the help documentation I only found the augmented sampling method for the MC algorithm. Thanks!

andrrizzi commented 2 years ago

Hi @jackzzs . REST2 typically works by partially softening intramolecular torsions and the interactions between ligand and receptor to reduce barriers between stable conformations. YANK only computes absolute free energies, however, and to do this, it removes the ligand-receptor interactions completely. You could in principle soften only partially the ligand by letting the lambda_sterics/torsions parameters not completely go to 0.0 in the alchemical protocol (see YAML input file documentation), but you won't get a meaningful free energy difference out of that calculation.