Blinded predictions of standard binding free energies: lessons learned from the SAMPL6 challenge

Journal of Computer-aided Molecular Design
Michail PapadourakisJulien Michel

Abstract

In the context of the SAMPL6 challenges, series of blinded predictions of standard binding free energies were made with the SOMD software for a dataset of 27 host-guest systems featuring two octa-acids hosts (OA and TEMOA) and a cucurbituril ring (CB8) host. Three different models were used, ModelA computes the free energy of binding based on a double annihilation technique; ModelB additionally takes into account long-range dispersion and standard state corrections; ModelC additionally introduces an empirical correction term derived from a regression analysis of SAMPL5 predictions previously made with SOMD. The performance of each model was evaluated with two different setups; buffer explicitly matches the ionic strength from the binding assays, whereas no-buffer merely neutralizes the host-guest net charge with counter-ions. ModelC/no-buffer shows the lowest mean-unsigned error for the overall dataset (MUE 1.29 < 1.39 < 1.50 kcal mol-1, 95% CI), while explicit modelling of the buffer improves significantly results for the CB8 host only. Correlation with experimental data ranges from excellent for the host TEMOA (R2 0.91 < 0.94 < 0.96), to poor for CB8 (R2 0.04 < 0.12 < 0.23). Further investigations indicate a pronounced depend...Continue Reading

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Citations

Jan 28, 2020·Journal of Computer-aided Molecular Design·Andrea RizziJohn D Chodera
Nov 12, 2018·Journal of Computer-aided Molecular Design·Andrea RizziJohn D Chodera
Apr 4, 2021·International Journal of Molecular Sciences·Esra Boz, Matthias Stein
Apr 23, 2021·Journal of Chemical Information and Modeling·Lauren NelsonDaniel J Cole
May 22, 2020·Journal of Chemical Information and Modeling·Maximilian KuhnJulien Michel
Oct 12, 2019·Journal of Chemical Theory and Computation·David R SlochowerMichael K Gilson
Oct 1, 2019·Journal of Chemical Theory and Computation·Anne C Leonhard, Jonathan K Whitmer
Jul 9, 2020·Journal of Chemical Information and Modeling·Jenke ScheenJulien Michel
Sep 1, 2021·Journal of Chemical Information and Modeling·Duván GonzálezEsteban Vöhringer-Martinez

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