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Accessing the applicability of polarized protein-specific charge in linear interaction energy analysis

Authors

  • Xiangyu Jia,

    1. State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai, China
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  • Juan Zeng,

    1. State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai, China
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  • John Z. H. Zhang,

    1. State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai, China
    2. NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, China
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  • Ye Mei

    Corresponding author
    1. State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai, China
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Abstract

The reliability of the linear interaction energy (LIE) depends on the atomic charge model used to delineate the Coulomb interaction between the ligand and its environment. In this work, the polarized protein-specific charge (PPC) implementing a recently proposed fitting scheme has been examined in the LIE calculations of the binding affinities for avidin and β-secretase binding complexes. This charge fitting scheme, termed delta restrained electrostatic potential, bypasses the prevalent numerical difficulty of rank deficiency in electrostatic-potential-based charge fitting methods via a dual-step fitting strategy. A remarkable consistency between the predicted binding affinities and the experimental measurement has been observed. This work serves as a direct evidence of PPC's applicability in rational drug design. © 2014 Wiley Periodicals, Inc.

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