title: Accessing the applicability of polarized protein-specific charge in linear interaction energy analysis.
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.
authors: State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai, 200062, China.
authors: Xiangyu
authors: X
authors: Jia
authors: Juan
authors: J
authors: Zeng
authors: John Z H
authors: JZ
authors: Zhang
authors: Ye
authors: Y
authors: Mei
mesh_terms: D008024:Ligands; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D008024:Ligands; D011506:Proteins
keywords: avidin; charge model; force field; linear interaction energy; polarization; β-secretase