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SAMPL6 host–guest blind predictions using a non equilibrium alchemical approach

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Abstract

In this paper, we compute, by means of a non equilibrium alchemical technique, called fast switching double annihilation methods (FSDAM), the absolute standard dissociation free energies of the the octa acids host–guest systems in the SAMPL6 challenge initiative. FSDAM is based on the production of canonical configurations of the bound and unbound states via enhanced sampling and on the subsequent generation of hundreds of fast non-equilibrium ligand annihilation trajectories. The annihilation free energies of the ligand when bound to the receptor and in bulk solvent are obtained from the collection of work values using an estimate based on the Crooks theorem for driven non equilibrium processes. The FSDAM blind prediction, relying on the normality assumption for the annihilation work distributions, ranked fairly well among the submitted blind predictions that were not adjusted with a linear corrections obtained from retrospective data on similar host guest systems. Improved results for FSDAM can be obtained by post-processing the work data assuming mixtures of normal components.

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Acknowledgements

We acknowledge the Partnership for Advance Computing in Europe (PRACE ) for awarding us access to Marconi-Broadwell and Marconi-KNL HPC platforms managed by the CINECA consortium (Italy). A part of the computing resources and the related technical support used for this work have been provided by CRESCO/ ENEAGRID HPC infrastructure and its staff; see http://www.cresco.enea.it for information.

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Authors and Affiliations

  1. Department of Chemistry, University of Florence, Via Lastruccia n. 3, 50019, Sesto Fiorentino, FI, Italy

    Piero Procacci

  2. CINECA-Interuniversity Consortium, via Magnanelli 6/3, 40033, Casalecchio di Reno, Bologna, Italy

    Massimiliano Guarrasi

  3. ENEA, Portici Research Centre, DTE-ICT-HPC, P.le E. Fermi, 1, 80055, Portici, NA, Italy

    Guido Guarnieri

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  1. Piero Procacci
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Correspondence to Piero Procacci.

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Procacci, P., Guarrasi, M. & Guarnieri, G. SAMPL6 host–guest blind predictions using a non equilibrium alchemical approach. J Comput Aided Mol Des 32, 965–982 (2018). https://doi.org/10.1007/s10822-018-0151-9

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