摘要
以β2肾上腺素受体(2β-AR)为模板,采用同源模建和分子动力学模拟构建了人类α1A-肾上腺素受体(α1A-AR)的三维结构模型,并利用PROCHECK,PROSA和WHAT-IF评估了模型的合理性.所得的结构采用分子对接程序Flexidock与激动剂去甲肾上腺素和拮抗剂西罗多辛分别进行对接,结果表明,2种配基具有相似的结合位点,配体可与同源模型的氨基酸残基Asp 106,Ser 188和Ser 192产生氢键作用,进一步证实了模型的合理性.研究结果对于基于受体的α1-AR的激动剂和拮抗剂的药物开发具有理论指导意义.
The three dimensional structure of human α1A-Adrenoceptors was modeled and refined using homology modeling and molecular dynamics simulation.The model was assessed by PROCHECK,PROSA and WHAT-IF methods,which confirmed that the obtained model was reliable.An agonist norepinephrine and an antagonist silodosin were docked into the refined structure by the molecular docking programs Flexidock.The results showed that the two ligands shared the similar binding cavity,which interact with the residues Asp106,Ser188 and Ser192 with H-bond.This work provides the theoretical guidance for the drug designing of agonist and antagonist of the α1A-Adrenoceptors for related diseases.
出处
《分子科学学报》
CAS
CSCD
北大核心
2011年第6期431-434,共4页
Journal of Molecular Science
基金
广州市科技计划重大专项资助(批准号:2009A1-E011-7)
