Absolute Binding Free Energies between T4 Lysozyme and 141 Small Molecules: Calculations Based on Multiple Rigid Receptor Configurations

J Chem Theory Comput. 2017 Jun 13;13(6):2930-2944. doi: 10.1021/acs.jctc.6b01183. Epub 2017 May 1.

Abstract

We demonstrate the feasibility of estimating protein-ligand binding free energies using multiple rigid receptor configurations. On the basis of T4 lysozyme snapshots extracted from six alchemical binding free energy calculations with a flexible receptor, binding free energies were estimated for a total of 141 ligands. For 24 ligands, the calculations reproduced flexible-receptor estimates with a correlation coefficient of 0.90 and a root-mean-square error of 1.59 kcal/mol. The accuracy of calculations based on Poisson-Boltzmann/surface area implicit solvent was comparable to that of previously reported free energy calculations.

MeSH terms

  • Bacteriophage T4 / enzymology*
  • Entropy
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation*
  • Muramidase / chemistry
  • Muramidase / metabolism*
  • Protein Binding
  • Protein Conformation
  • Small Molecule Libraries / metabolism*

Substances

  • Small Molecule Libraries
  • Muramidase