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Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
SiMMap: a web server for inferring site-moiety map to recognize interaction preferences between protein pockets and
Yen-Fu Chen1, Kai-Cheng Hsu, Shen-Rong Lin
1Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 30050, Taiwan.
Abstract:
The protein-ligand interacting mechanism is essential to biological processes and drug discovery. The SiMMap server statistically derives site-moiety map with several anchors, which describe the relationship between the moiety preferences and physico-chemical properties of the binding site, from the interaction profiles between query target protein and its docked (or co-crystallized) compounds. Each anchor includes three basic elements: a binding pocket with conserved interacting residues, the moiety composition of query compounds and pocket-moiety interaction type (electrostatic, hydrogen bonding or van der Waals). We provide initial validation of the site-moiety map on three targets, thymidine kinase, and estrogen receptors of antagonists and agonists. Experimental results show that an anchor is often a hot spot and the site-moiety map can help to assemble potential leads by optimal steric, hydrogen bonding and electronic moieties. When a compound highly agrees with anchors of site-moiety map, this compound often activates or inhibits the target protein. We believe that the site-moiety map is useful for drug discovery and understanding biological mechanisms. The SiMMap web server is available at http://simfam.life.nctu.edu.tw/.
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