SiMMap: a web server for inferring site-moiety map to recognize interaction preferences between protein pockets and compound moieties.
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/.
Chen
Yen-Fu
YF
Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 30050, Taiwan.
Hsu
Kai-Cheng
KC
Lin
Shen-Rong
SR
Wang
Wen-Ching
WC
Huang
Yu-Chi
YC
Yang
Jinn-Moon
JM
D001665:Binding Sites; D055808:Drug Discovery; D020407:Internet; D008024:Ligands; D011506:Proteins / Q000737:chemistry*; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry; D012984:Software; D013937:Thymidine Kinase / Q000737:chemistry; D014584:User-Computer Interface
D008024:Ligands; D011506:Proteins; D011960:Receptors, Estrogen; D013937:Thymidine Kinase