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BEDAM binding free energy predictions for the SAMPL4 octa-acid host challenge

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Abstract

The binding energy distribution analysis method (BEDAM) protocol has been employed as part of the SAMPL4 blind challenge to predict the binding free energies of a set of octa-acid host–guest complexes. The resulting predictions were consistently judged as some of the most accurate predictions in this category of the SAMPL4 challenge in terms of quantitative accuracy and statistical correlation relative to the experimental values, which were not known at the time the predictions were made. The work has been conducted as part of a hands-on graduate class laboratory session. Collectively the students, aided by automated setup and analysis tools, performed the bulk of the calculations and the numerical and structural analysis. The success of the experiment confirms the reliability of the BEDAM methodology and it shows that physics-based atomistic binding free energy estimation models, when properly streamlined and automated, can be successfully employed by non-specialists.

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Acknowledgments

This work has been supported in part by research grants from the National Institute of Health (GM30580) and the National Science Foundation Cyber-enabled Discovery and Innovation Award (CHE-1125332). The calculations reported in this work have been performed at the BioMaPS High Performance Computing Center at Rutgers University funded in part by the NIH shared instrumentation Grants No. 1 S10 RR022375. We gratefully acknowledge Lauren Wickstrom for helpful discussion during the preparation of the manuscript.

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Authors and Affiliations

  1. Department of Chemistry, CUNY Brooklyn College, 2900 Bedford Avenue, Brooklyn, NY, 11210, USA

    Emilio Gallicchio

  2. Department of Chemistry and Chemical Biology, Rutgers the State University of New Jersey, Piscataway, NJ, 08854, USA

    Haoyuan Chen, He Chen, Michael Fitzgerald, Yang Gao, Malathi Kalyanikar, Chuan Kao, Beidi Lu, Yijie Niu, Manasi Pethe & Jie Zhu

  3. Center for Biophysics and Computational Biology, Institute of Computational Molecular Science, Temple University, Philadelphia, PA, USA

    Peng He & Ronald M. Levy

  4. Department of Chemistry, Temple University, Philadelphia, PA, USA

    Peng He & Ronald M. Levy

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  1. Emilio Gallicchio
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Correspondence to Emilio Gallicchio.

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Gallicchio, E., Chen, H., Chen, H. et al. BEDAM binding free energy predictions for the SAMPL4 octa-acid host challenge. J Comput Aided Mol Des 29, 315–325 (2015). https://doi.org/10.1007/s10822-014-9795-2

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