摘要
目的本研究采用比较分子力场分析法(comparative molecular field analysis,CoMFA)和比较分子相似性指数分析法(comparative molecular similarity indices analysis,CoMSIA),系统研究了30个1,3-二氢苯并[b][1,4]二氮杂卓-2-酮类非竞争性代谢型谷氨酸受体2/3(mGluR2/3)拮抗剂的三维定量构效关系。方法通过考察网格点步长对CoMFA研究统计结果和各种分子场组合、网格点步长和衰减因子对CoMSIA研究统计结果的影响,建立了3D-QSAR模型,发现立体场、静电场、疏水场和氢键受体场的组合可得到最佳模型。结果所建立的CoMFA和CoMSIA模型的交叉相关系数q2值分别为0.729和0.713,均具有较强的预测能力。结论利用CoMFA和CoMSIA模型的三维等值线图直观地解释了化合物的构效关系,阐明了化合物结构与生物活性的关系,为进一步结构设计和优化提供了重要依据。
Objective Using comparative molecular field analysis （CoMFA）and comparative molecular similarity indices analysis （ CoMSIA）, three dimensional structure-activity relationship （3D-QSAR） had been studied on a series of 1,3-dihydrobenzo [b] [1,4] diazepin-2-one compounds. Methods Variation of grid spacing was used during the optimization of the CoMFA model. For CoMSIA study, the influence of the combination of different field types was evaluated and the best combination was considered to be of steric, electrostatic, hydrophobic and H-bonding acceptor fields. Variation of grid spacing and attenuation factor was used to get the best CoMSIA model. Results The resulting CoMFA and CoMSIA models had a cross validated coefficient q^2 of 0.729and 0. 713 respectively, which showed strong predictive ability on both test set and training set. Conclusion The 3D contour maps of CoMFA and CoMSIA provide smooth and interpretable explanation of the structure and activity relationship for the compounds, which will guide the design of novel mGluR2/3 antagonists with relatively high activity.
出处
《同济大学学报（医学版）》
CAS
2008年第4期61-65,共5页
Journal of Tongji University(Medical Science)
基金
上海市重点学科建设资助项目(B906)
