Absolute Binding Free Energy Calculations for Buried Water Molecules

• DOI: 10.1021/acs.jctc.2c00658
• Publication Date: 2022-10-05T15:10:42Z
• Authors: Yunhui Ge; Hannah M. Baumann; David L. Mobley
• Keywords: Thermodynamic integration

Water often plays a key role in mediating protein-ligand interactions. Understanding contributions from active-site water molecules to binding thermodynamics of ligand is important predicting free energies for optimization. In this work, we tested non-equilibrium switching method absolute energy calculations on sites 13 systems. We discuss the lessons learned about identified issues that affected our and ways address them. This work fits with larger focus how do accurate when rearrangements are very slow, such as due modification (as relative calculations) or calculations). The studied can potentially be used account limited sampling via providing endpoint corrections using calculated water.