Accessing the applicability of polarized protein-specific charge in linear interaction energy analysis
Article first published online: 5 FEB 2014
Copyright © 2014 Wiley Periodicals, Inc.
Journal of Computational Chemistry
Volume 35, Issue 9, pages 737–747, 5 April 2014
How to Cite
How to cite this article: J. Comput. Chem. 2014, 35, 737–747. DOI: 10.1002/jcc.23547, , , .
- Issue published online: 25 FEB 2014
- Article first published online: 5 FEB 2014
- Manuscript Accepted: 5 JAN 2014
- Manuscript Revised: 15 NOV 2013
- Manuscript Received: 15 SEP 2013
- National Natural Science Foundation of China. Grant Number: 10974054, 20933002, 21173082
- The Shanghai PuJiang Program. Grant Number: 09PJ1404000
- linear interaction energy;
- force field;
- charge model;
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.