摘要
通过SYBYL X 2.0软件包中Topomer CoMFA和Surflex-dock研究28种黄嘌呤结构的胞浆型磷酸烯醇式丙酮酸羧激酶（cPEPCK）抑制剂的三维定量构效关系（3D-QSAR）和分子对接模式.所得优化的3D-QSAR模型q2和r^2分别为0.907和0.994（q^2〉0.5时,建立的模型具有可靠的预测能力）,结果表明该模型具有较高预测能力.分子对接结果显示,此类分子与cPEPCK的Asn 533,Asn 292和Phe 530等活性功能残基具有氢键作用.Trp516可能是潜在的活性残基.基于以上研究讨论,为设计和开发具有较高活性的新型黄嘌呤类cPEPCK抑制剂提供有效信息.
This study explored three-dimensional quantitative structure-activity relationship（3 DQSAR）and molecular docking model of 28 cPEPCK inhibitors involving in xanthine structure using the Topomer CoMFA module and the Surflex-dock module in the SYBYL-X 2.0 package.One satisfactory substructure-based Topomer CoMFA model（q^2=0.907;r^2=0.944）possessing predictive capability was obtained.The molecular docking results showed that these molecules had hydrogen bonding with the active functional residues of cPEPCK such as Asn 533,Asn 292 and Phe 530.Trp516 might be a potential active residue.Based on the results,this study can provide effective information for the design and development of novel xanthine derivatives with higher cPEPCK inhibitory activity.
作者
刘景陶
王晓
倪敬轩
毕毅
LIU Jing-tao;WANG Xiao;NI Jing-xuan;BI Yi(Department of Physiology, Hetao University, Bayannur 015000, China;School of Pharmacy, Yantai University, Yantai 264005, China)
出处
《分子科学学报》
CAS
CSCD
北大核心
2018年第3期258-264,共7页
Journal of Molecular Science
基金
河套学院自然科学重点项目(HYZZ201501)
