Use of the Multilayer Fragment Molecular Orbital Method to Predict the Rank Order of Protein-Ligand Binding Affinities: A Case Study Using Tankyrase 2 Inhibitors.

ABSTRACT: In computational drug discovery, ranking a series of compound analogues in the order that is consistent with the experimental binding affinities remains a challenge. Many of the computational methods available for evaluating binding affinities have adopted molecular mechanics (MM)-based force fields, although they cannot completely describe protein-ligand interactions. By contrast, quantum mechanics (QM) calculations play an important role in understanding the protein-ligand interactions; however, their huge computational costs hinder their application in drug discovery. In this study, we have evaluated the ability to rank the binding affinities of tankyrase 2 ligands by combining both MM and QM calculations. Our computational approach uses the protein-ligand binding energies obtained from

SUBMITTER: Okimoto N 

PROVIDER: S-EPMC6641631 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature