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Ligand binding affinity prediction by linear interaction energy methods

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Abstract

A recent method for estimating ligand binding affinities is extended. This method employs averages of interaction potential energy terms from molecular dynamics simulations or other thermal conformational sampling techniques. Incorporation of systematic deviations from electrostatic linear response, derived from free energy perturbation studies, into the absolute binding free energy expression significantly enhances the accuracy of the approach. This type of method may be useful for computational prediction of ligand binding strengths, e.g., in drug design applications.

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Authors and Affiliations

  1. Department of Molecular Biology, Uppsala University, Biomedical Centre, Box 590, S-751 24, Uppsala, Sweden

    Tomas Hansson, John Marelius & Johan Åqvist

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  1. Tomas Hansson
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  2. John Marelius
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  3. Johan Åqvist
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Hansson, T., Marelius, J. & Åqvist, J. Ligand binding affinity prediction by linear interaction energy methods. J Comput Aided Mol Des 12, 27–35 (1998). https://doi.org/10.1023/A:1007930623000

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