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Exponential Repulsion Improves Structural Predictability of Molecular Docking

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    0467239 - ÚEB 2017 RIV US eng J - Journal Article
    Bazgier, Václav - Berka, K. - Otyepka, M. - Banáš, P.
    Exponential Repulsion Improves Structural Predictability of Molecular Docking.
    Journal of Computational Chemistry. Roč. 37, č. 28 (2016), s. 2485-2494. ISSN 0192-8651
    Institutional support: RVO:61389030
    Keywords : cyclin-dependent kinases * structure-based design * scoring functions * cdk2 inhibitors * force-field * ligand interactions * drug discovery * purine * potent * protein-kinase-2 * molecular docking * dock 6.6 * drug design * cyclin-dependent kinase 2 * directory of decoys
    Subject RIV: CF - Physical ; Theoretical Chemistry
    Impact factor: 3.229, year: 2016

    Molecular docking is a powerful tool for theoretical prediction of the preferred conformation and orientation of small molecules within protein active sites. The obtained poses can be used for estimation of binding energies, which indicate the inhibition effect of designed inhibitors, and therefore might be used for in silico drug design. However, the evaluation of ligand binding affinity critically depends on successful prediction of the native binding mode. Contemporary docking methods are often based on scoring functions derived from molecular mechanical potentials. In such potentials, nonbonded interactions are typically represented by electrostatic interactions between atom-centered partial charges and standard 6-12 Lennard-Jones potential. Here, we present implementation and testing of a scoring function based on more physically justified exponential repulsion instead of the standard Lennard-Jones potential. We found that this scoring function significantly improved prediction of the native binding modes in proteins bearing narrow active sites such as serine proteases and kinases.
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