Author(s): Chen, CYC (Chen, Calvin Yu-Chian)
Title: Computational screening and design of traditional Chinese medicine (TCM) to block phosphodiesterase-5
Source: JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 28 (3): 261-269 OCT 2009 Language: English
Document Type: Article
Author Keywords: Phosphodiesterase-5 (PDE-5); Traditional Chinese medicines (TCM);
Erectile dysfunction; Multiple linear regressions (MLR); Pharmacophore analysis KeyWords Plus: PHARMACOINFORMATICS APPROACH; PHARMACOPHORE ANALYSIS; DERIVATIVES; INHIBITORS; PDE5; SUANZAOREN; DISCOVERY;
RECEPTOR; BINDING
Abstract: The traditional Chinese medicines (TCM), Epimedium sagittatum (ESs), Cnidium monnieri (CMs), and Semen cuscutae (SCs), were used for treating erectile dysfunction since the ancient Han dynasty (202 BC-AD 220). Phosphodiesterase-5 (PDE-5) is deemed the target protein for inhibition to treat erectile dysfunction. In this study, a reliable multiple linear regression (MLR) model (r value = 0.8484) was used to predict the activities of new
candidates which were designed from ES, CM, and SC. From docking and pharmacophore analysis, the potent candidates among ES, CM, and SC were screened. SC01, SC03, and ES03b were predicted to have high potencies based on MLR analysis and high docking scores. Additionally, from our analysis, we make the follow conclusion (1) Hydrophobic compounds tend to be more potent PDE-5 inhibitors; (2) Because of the big binding site, inhibitors with molecular weights over 500 remain potent; (3) From the pharmacophore analysis, the features of hydrogen bond acceptors are the basis for designing novel inhibitors of PDE-5 and (4) According to MLR analysis, the number of ring groups could be up to 6, but the number of aromatic rings was limited to 4 to be potent. This study offers an alternative way to screen PDE-5 inhibitors from TCM and provides a scientific basis for confirming
pharmacological actions of TCM. (C) 2009 Elsevier Inc. All rights reserved.
Addresses: [Chen, Calvin Yu-Chian] China Med Univ, Sch Chinese Med, Lab
Pharmacoinformat & Nanotechnol, Taichung 40402, Taiwan; [Chen, Calvin Yu-Chian] Asia Univ, Dept Bioinformat, Taichung 41354, Taiwan
Reprint Address: Chen, CYC, MIT, Dept Computat & Syst Biol, 77 Massachusetts Ave, 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 CMU 97-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 (CMU 97-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 of China Medical University.
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Publisher: ELSEVIER SCIENCE INC
Publisher Address: 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA ISSN: 1093-3263
DOI: 10.1016/j.jmgm.2009.08.004
29-char Source Abbrev.: J MOL GRAPH MODEL ISO Source Abbrev.: J. Mol. Graph.
Source Item Page Count: 9
Subject Category: Biochemical Research Methods; Biochemistry & Molecular Biology;
Computer Science, Interdisciplinary Applications; Crystallography; Mathematical &
Computational Biology
ISI Document Delivery No.: 513UL
