Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 30050, Taiwan.
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W424-30. doi: 10.1093/nar/gkq480. Epub 2010 Jun 2.
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/.
蛋白质-配体相互作用机制对于生物过程和药物发现至关重要。SiMMap 服务器从查询目标蛋白与其对接（或共结晶）化合物之间的相互作用谱中，通过几个锚点统计推导出位点-基团图谱，这些锚点描述了基团偏好与结合位点物理化学性质之间的关系。每个锚点都包含三个基本元素：一个具有保守相互作用残基的结合口袋、查询化合物的基团组成和口袋-基团相互作用类型（静电、氢键或范德华力）。我们在三个靶标（胸苷激酶和拮抗剂和激动剂的雌激素受体）上对位点-基团图谱进行了初步验证。实验结果表明，一个锚点通常是一个热点，而位点-基团图谱可以通过最佳的空间、氢键和电子基团帮助组装潜在的先导化合物。当一个化合物与位点-基团图谱的锚点高度吻合时，该化合物通常会激活或抑制靶标蛋白。我们相信位点-基团图谱对于药物发现和理解生物机制是有用的。SiMMap 网络服务器可在 http://simfam.life.nctu.edu.tw/ 获得。
