中文摘要：

基于计算生物学方法对61个ROCK激酶靶标分子建立三维定量构效关系（3DQSAR）模型.在基于配体叠合的基础上,发现CoMSIA中2个场组合（位阻场和疏水场）为最好的模型（Q2=0.509,R2ncv=0.987,SEE=0.131,F=287.999和R2pre=0.837）.基于此模型基础上的三维等势线图形象地说明了在各个位置增加疏水性的大取代基或者亲水性基团有利于提高分子的生物活性.此外,分子对接模拟结果显示了氨基酸Glu170,Met172和Asp232在受体调节剂中发挥着重要作用.这些结果能够帮助深入了解ROCK激酶的作用机理,并且能够为今后的药物设计提供新的方向.

英文摘要：

For the first time,via comparative molecular field analysis（CoMFA）and comparative molecular similarity indices analysis（CoMSIA）,a set of ligand-and receptor-based 3D-QSAR models were carried out to explore the structure-activity correlation of 61 ROCK promising inhibitors.Based on the ligand-based alignment,an optimal CoMSIA model（SH）was obtained with good predictive power of Q2=0.509,R2ncv=0.987,SEE=0.131,F=287.999 and R2pred=0.837.The 3Dcontour maps suggested that the compounds substituted on special position with bulky hydrophobic or hydrophilic groups can enhance the biological activity.Furthermore,the docking analysis showed that Glu170,Met172 and Asp232which formed three H-bonds are crucial for ROCK receptor.The present work provides useful guidelines for future structural modifications of this class of compounds,which would assist the development of superior ROCK inhibitors.