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CPT Pharmacometrics Syst Pharmacol. 2018 Jan;7(1):16-25. doi: 10.1002/psp4.12253. Epub 2017 Nov 20.

Network-Wide Screen Identifies Variation of Novel Precise On-Module Targets Using Conformational Modudaoism.

Author information

1
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
2
Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
3
ShanXi Buchang Pharmaceutical Co., Ltd., Heze, China.
4
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
5
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
6
Department of Mathematics, School of Science, Beijing Jiaotong University, Beijing, China.

Abstract

Modular targeting is promising in drug research at the network level, but it is challenging to quantificationally identify the precise on-modules. Based on a proposed Modudaoism (MD), we defined conserved MD (MDc) and varied MD (MDv) to quantitatively evaluate the conformational and energy variations of modules, and thereby identify the conserved and discrepant allosteric modules (AMs). Compared to the Zsummary , MDc/MDv got an optimized result of module preserved ratio and modular structure. In the mice anti-ischemic networks, 3, 5, and 1 conserved AMs as well as 4, 1, and 3 on-modules of baicalin (BA), jasminoidin (JA), and ursodeoxycholic acid (UA) were identified by MDc and MDv, 5 unique AMs and their characteristic actions were revealed. Besides, co-immunoprecipitation (Co-IP) experiments validated the representative modular structure. MDc/MDv method can quantitatively define the conformational variations of modules and screen the precise on-modules network-wide, which may provide a promising strategy for drug discovery.

PMID:
28925077
PMCID:
PMC5784734
DOI:
10.1002/psp4.12253
[Indexed for MEDLINE]
Free PMC Article

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