Author(s): Chen, CYC (Chen, Calvin Yu-Chian)
Title: Weighted Equation and Rules - A Novel Concept for Evaluating Protein-Ligand Interaction
Source: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 27 (3): 271-282 DEC 2009
Language: English Document Type: Article
Author Keywords: Weighted rules; Yin-Yang; Weighted score (WS); Human Epidermal growth factor Receptor 2 (HER2); Scoring function; Consensus score (CS)
KeyWords Plus: PYRROLOTRIAZINE DUAL INHIBITORS; HER2 TYROSINE KINASE; DE- NOVO DESIGN; PHARMACOPHORE ANALYSIS; DRUG DISCOVERY;
PHARMACOINFORMATICS APPROACH; MOLECULAR-DYNAMICS; FLEXIBLE DOCKING;
SCORING FUNCTION; EGFR
Abstract: In this study, a novel methodology for evaluating protein-ligand interaction and quantitated the traditional Chinese medicine (TCM) by Yin-Yang theory are proposed and investigated by a case report of the human epidermal growth factor receptor 2 (HER2)-ligand.
Inhibitors (n = 176) of HER2 from references with a broad range of activities (IC50) were employed to the docking program to calculate the binding affinities. The docking score of twelve scoring functions versus actual pIC(50) plot were regressed. According to the weighted rules, the coefficient of determinations (R-2) from the regression analysis of each scoring function and pIC(50) were chosen as the weights in the weighted equation. The R-2 (0.5858) of weighted score (WS) versus actual pIC(50), was statistically higher than that of the
consensus score (CS) (R-2 = 0.2441). The WS method lies in combining the scoring functions from different algorithms to evaluate the sum of binding affinities that is more comprehensive than any single scoring function can achieve. The WS calculated by equation successfully shows a statically significant correlation with good predictability. Thus, this methodology might provide a persuasive virtual screening criterion to evaluate the protein-ligand interaction and quantitative analysis of the functions for Chinese medicine in the future.
Addresses: [Chen, Calvin Yu-Chian] China Med Univ Hosp, Terry Fox Canc Res Lab, Taichung 40402, Taiwan; [Chen, Calvin Yu-Chian] Asia Univ, Dept Bioinformat, Taichung 41354, Taiwan; [Chen, Calvin Yu-Chian] China Med Univ, Lab Pharmacoinformat &
Nanotechnol, Sch Chinese Med, Taichung 40402, Taiwan
Reprint Address: Chen, CYC, MIT, Dept Computat & Syst Biol, Cambridge, MA 02139 USA.
E-mail Address: [email protected] Funding Acknowledgement:
Funding Agency Grant Number
National Science Council of China NSC 98-2221-E-039-007-
China Medical University CMU97-CMC-014 CMU97-276
The research was supported by grants from the National Science Council of China (NSC 98- 2221-E-039-007-) and China Medical University (CMU97-CMC-014, CMU97-276). I am grateful to the National Center for High-performance Computing for computer time and facilities and professional suggestion by Drs. Chung Y. Hsu and Sarina Hui-Lin Chien of China Medical University. I also thanks to Dr. Ying-shiung Lee for the inspiration of Yin- Yang's concept for me to build this computational algorithm of protein-ligand interaction.
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Publisher: ADENINE PRESS
Publisher Address: 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA ISSN: 0739-1102
29-char Source Abbrev.: J BIOMOL STRUCT DYN ISO Source Abbrev.: J. Biomol. Struct. Dyn.
Source Item Page Count: 12
Subject Category: Biochemistry & Molecular Biology; Biophysics
ISI Document Delivery No.: 513EX
