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Frontiers in Molecular Biosciences
Article . 2022 . Peer-reviewed
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PubMed Central
Other literature type . 2022
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Assessing the effect of forcefield parameter sets on the accuracy of relative binding free energy calculations

Authors: Shan Sun; David J. Huggins; David J. Huggins;

Assessing the effect of forcefield parameter sets on the accuracy of relative binding free energy calculations

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.

Keywords

validation, relative binding free energy, QH301-705.5, forcefield, Molecular Biosciences, free energy perturbation (FEP), Biology (General), OpenMM

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
11
Top 10%
Average
Top 10%
Green
gold