Expanded Ensemble Predictions of Absolute Binding Free Energies in the SAMPL9 Host-guest Challenge

Overview

Journal Phys Chem Chem Phys

Publisher Royal Society of Chemistry

Specialties Biophysics
Chemistry

Date 2023 Nov 27

PMID 38009066

Authors

Matthew F D Hurley

Robert M Raddi

Jason G Pattis

Vincent A Voelz

Affiliations

Soon will be listed here.

Abstract

As part of the SAMPL9 community-wide blind host-guest challenge, we implemented an expanded ensemble workflow to predict absolute binding free energies for 13 small molecules against pillar[6]arene. Notable features of our protocol include consideration of a variety of protonation and enantiomeric states for both host and guests, optimization of alchemical intermediates, and analysis of free energy estimates and their uncertainty using large numbers of simulation replicates performed using distributed computing. Our predictions of absolute binding free energies resulted in a mean absolute error of 2.29 kcal mol and an of 0.54. Overall, results show that expanded ensemble calculations using all-atom molecular dynamics simulations are a valuable and efficient computational tool in predicting absolute binding free energies.

Citing Articles

The SAMPL9 host-guest blind challenge: an overview of binding free energy predictive accuracy.

Amezcua M, Setiadi J, Mobley D Phys Chem Chem Phys. 2024; 26(12):9207-9225.

PMID: 38444308 PMC: 10954238. DOI: 10.1039/d3cp05111k.

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