Author(s): Chen, CYC (Chen, Calvin Yu-Chian)
Title: Virtual Screening and Drug Design for PDE-5 Receptor from Traditional Chinese Medicine Database
Source: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 27 (5): 627-640 APR 2010
Language: English Document Type: Article
Author Keywords: Erectile dysfunction (ED); Phosphodiesterase type-5 (PDE-5); Traditional Chinese medicine (TCM); Docking; Three dimensional quantitative structure-activity
relationship (3D QSAR)
KeyWords Plus: CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; ERECTILE DYSFUNCTION; PHARMACOPHORE ANALYSIS; MOLECULAR DOCKING;
PHARMACOINFORMATICS APPROACH; FLEXIBLE DOCKING; PENILE ERECTION;
NITRIC-OXIDE; V3 LOOP; INHIBITORS
Abstract: Erectile dysfunction (ED) is a sexual disorder mainly caused by decrease in cellular concentration of cyclic guanosine monophosphate (cGMP), which is degraded by
phosphodiesterase type-5 (PDE-5). As a potent therapeutic target, inhibitors such as Viagra (R), Cialis (R), and Levitra (R) have already been developed to target PDE-5 for treating ED;
traditional Chinese medicine, Epimedium sagittatum. also has shown prominent results as well. To developed new PDE-5 inhibitors, we performed a virtual screening of traditional Chinese medicine (TCM) database and docking analyses to identify candidates. Known PDE- 5 inhibitors were used to construct a three dimensional quantitative structure-activity
relationship (3D QSAR) model by HypoGen program. From docking analyses, isochlorogenic acid b was identified as the most potential inhibitory compound. De novo evolution designed 47 derivatives. Of the 47 derivatives, seven were able to map into the pharmacophore model.
and these seven compounds were suggested to be the most promising leads for inhibiting PDE-5. An analysis of the hydrogen bond interactions formed between the docked ligands and PDE-5 identified ASN662, SER663 and GLN817 as the most frequently interacting residues. A total of eight novel leading compounds were identified to have favorable interaction with PDE- 5. These compounds all had hydrogen bond interactions with three key residues that could be further investigated for understanding of PDE-5 and ligands interaction.
Addresses: [Chen, Calvin Yu-Chian] China Med Univ, Sch Chinese Med, Lab Computat &
Syst Biol, Taichung 40402, Taiwan; [Chen, Calvin Yu-Chian] Asia Univ, Dept Bioinformat, Taichung 41354, Taiwan
Reprint Address: Chen, CYC, MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
E-mail Address: [email protected] Funding Acknowledgement:
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.
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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: 14
Subject Category: Biochemistry & Molecular Biology; Biophysics ISI Document Delivery No.: 553GW
