Combining Alchemical Transformation with a Physical Pathway to Accelerate Absolute Binding Free Energy Calculations of Charged Ligands to Enclosed Binding Sites.

ABSTRACT: We present a new approach to more accurately and efficiently compute the absolute binding free energy for receptor-ligand complexes. Currently, the double decoupling method (DDM) and the potential of mean force method (PMF) are widely used to compute the absolute binding free energy of biomolecular complexes. DDM relies on alchemically decoupling the ligand from its environments, which can be computationally challenging for large ligands and charged ligands because of the large magnitude of the decoupling free energies involved. In contrast, the PMF method uses a physical pathway to directly transfer the ligand from solution to the receptor binding pocket and thus avoids some of the aforementioned problems in DDM. However, the PMF method has its own drawbacks: because of its reliance on a

SUBMITTER: Cruz J 

PROVIDER: S-EPMC7269639 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature