Comparing alchemical and physical pathway methods for computing the absolute binding free energy of charged ligands.

ABSTRACT: Accurately predicting absolute binding free energies of protein-ligand complexes is important as a fundamental problem in both computational biophysics and pharmaceutical discovery. Calculating binding free energies for charged ligands is generally considered to be challenging because of the strong electrostatic interactions between the ligand and its environment in aqueous solution. In this work, we compare the performance of the potential of mean force (PMF) method and the double decoupling method (DDM) for computing absolute binding free energies for charged ligands. We first clarify an unresolved issue concerning the explicit use of the binding site volume to define the complexed state in DDM together with the use of harmonic restraints. We also provide an alternative derivation for th

SUBMITTER: Deng N 

PROVIDER: S-EPMC6061996 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature