绿原酸、3,4-二咖啡酰奎宁酸、3,5-二咖啡酰奎宁酸与人白蛋白的分子对接研究  

Molecular docking of chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid with human serum albumin

作　　者：周婧[1] 马宏跃[1] 范欣生[1] 萧伟[2,3] 王团结[2,3] 

机构地区：[1]南京中医药大学药学院,江苏省方剂研究重点实验室,江苏南京201146 [2]江苏康缘药业股份有限公司,江苏连云港222001 [3]中药制药过程新技术国家重点实验室(筹),江苏连云港222001

出　　处：《中西医结合学报》2012年第10期1149-1154,共6页Journal of Chinese Integrative Medicine

基　　金：南京中医药大学中医学一级学科开放课题资助(No.YS2012ZYX311);中药制药过程新技术国家重点实验室开放课题(No.SKL2010Z0404);江苏省中医药局康缘中医药科技创新基金(No.HZ1007KY);江苏高校优势学科建设工程资助项目

摘　　要：目的:比较可疑致敏原绿原酸、异绿原酸与人血清白蛋白(human serum albumin,HSA)的分子结合模式和结合能力。方法:采用Molegro Virtual Docker(MVD)软件,以华法令、地西泮和HSA共结晶复合物作为受体模板,比较绿原酸和异绿原酸(3,4-二咖啡酰奎宁酸、3,5-二咖啡酰奎宁酸)在HSA载药位点Ⅰ和Ⅱ的分子对接情况,以对接评分、关键氨基酸基团和氢键作用确定分子的结合模式。结果:绿原酸、3,4-二咖啡酰奎宁酸和3,5-二咖啡酰奎宁酸在HSA位点Ⅰ的分子对接分值为-112.3、-155.3和-153.1,在HSA位点Ⅱ的对接分值为-101.7、-138.5和-133.4。在位点Ⅰ,两个异绿原酸分子与关键脂溶性基团Ala291和Leu238的疏水力明显大于绿原酸;异绿原酸、绿原酸与该位点入口和内部不同的极性氨基酸基团形成氢键;与绿原酸分子相比,异绿原酸的第2个咖啡酰基占居该位点右侧亲脂区。在位点Ⅱ,异绿原酸的第2个咖啡酰基增加了其与极性氨基酸的作用。结论:异绿原酸与绿原酸相比,有更高的HSA分子对接评分,其多出的一个咖啡酰基增加了与HSA载药位点的结合能力。To investigate the mechanism of binding of human serum albumin （HSA） with potential sensitinogen, including chlorogenic acid and two isochlorogenic acids （3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid）. METHODS： By using the docking algorithm of computer-aided molecular design and the Molegro Virtual Docker, the crystal structures of HSA with warfarin and diazepam （Protein Data Bank ID： 2BXD and 2BXF） were selected as molecular docking receptors of HSA sites Ⅰ and Ⅱ. According to docking scores, key residues and H- bond, the molecular docking mode was selected and confirmed. The molecular docking of chlorogenic acid and two isochlorogenic acids on sites Ⅰand Ⅱ was compared based on the above design. RESULTS： The results from molecular docking indicated that chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid could bind to HSA site Ⅰ by high affinity scores of --112.3, --155.3 and --153.1, respectively. They could bind to site Ⅱ on HSA by high affinity scores of -101.7, -138.5 and -133.4, respectively. In site Ⅰ, two isochlorogenic acids interacted with the key apolar side-chains of Leu238 and Ala291 by higher affinity scores than chlorogenic acid. Furthermore, the H-bonds of isochlorogenic acids with polar residues inside the pocket and at the entrance of the pocket were different from chlorogenic acid. Moreover, the second coffee acyl of isochlorogenic acid occupied the right-hand apolar compartment in the pocket of HSA site Ⅰ. In site Ⅱ, the second coffee acyl of isochlorogenic acid formed the H-bonds with polar side-chains, which contributed isochlorogenic acid to binding with site Ⅱ of HSA. CONCLUSION： The isochlorogenic acids with two coffee acyls have higher binding abilities with HSA than chlorogenic acid with one coffee acyl, suggesting that isochlorogenic acids binding with HSA may be sensitinogen.

关 键 词：植物提取物 绿原酸 异绿原酸 白蛋白 分子对接 计算机辅助设计 

分 类 号：R96[医药卫生—药理学]