Assessing the effect of forcefield parameter sets on the accuracy of relative binding free energy calculations. Academic Article uri icon

Overview

abstract

  • Software for accurate prediction of protein-ligand binding affinity can be a key enabling tool for small molecule drug discovery. Free energy perturbation (FEP) is a computational technique that can be used to compute binding affinity differences between molecules in a congeneric series. It has shown promise in reliably generating accurate predictions and is now widely used in the pharmaceutical industry. However, the high computational cost and use of commercial software, together with the technical challenges to setup, run, and analyze the simulations, limits the usage of FEP. Here, we use an automated FEP workflow which uses the open-source OpenMM package. To enable effective application of FEP, we compared the performance of different water models, partial charge assignments, and AMBER protein forcefields in eight benchmark test cases previously assembled for FEP validation studies.

publication date

  • September 12, 2022

Identity

PubMed Central ID

  • PMC9549959

Scopus Document Identifier

  • 36849122972

Digital Object Identifier (DOI)

  • 10.1063/1.1740409

PubMed ID

  • 36225254

Additional Document Info

volume

  • 9