删除或更新信息,请邮件至freekaoyan#163.com(#换成@)

2,4-二氨基嘧啶类FAK抑制剂的3D-QSAR研究

本站小编 Free考研考试/2021-12-27

手机快速免费注册会员,立即获取本站资料解压缩密码!
中文关键词:FAK抑制剂2,4-二氨基嘧啶类3D-QSAR模型优化分子对接 英文关键词:FAK inhibitor2,4-diaminopyrimidines3D-QSARModel optimizationMolecular docking 基金项目:贵州省科技厅联合项目(黔科合平台人才[2018]5779-13/75)、贵州省教育厅青年人才成长项目([2018]174)和贵州省科技厅基础研究计划项目(黔科合基础[2020]1Z008)资助 摘要点击次数:118 全文下载次数:0 中文摘要: 摘要 本文选取42个2,4-二氨基嘧啶类FAK小分子抑制剂,分别以比较分子场分析法(CoMFA)与相似性指数分析法(CoMSIA)构建3D-QSAR模型,评价模板分子、公共骨架点、最小能量优化参数、分子构象等因素对模型优化的影响。分析最优模型中立体场、静电场以及氢键等因素对抑制剂活性的影响,并应用分子对接分析该类抑制剂与FAK蛋白的相互作用。结果表明选择16号化合物作为模板分子,骨架A作为公共骨架点,最小能量优化参数中电荷、最大迭代系数、最低能量限定值分别为MMFF94、1000、0.01 Kcal/mol时所构建的模型最优。以CoMFA和CoMSIA构建的3D-QSAR模型的交叉验证系数(q2)分别为0.666和0.736,非交叉验证系数(R2)分别为0.990和0.989,表明此模型具有良好的预测能力。分子对接分析显示,其与FAK的氨基酸残基CYS502、ASP564形成了重要的氢键作用,并与周围残基形成了较强的疏水作用。通过3D-QSAR的构建与分子对接分析,可指导2,4-二氨基嘧啶类FAK小分子抑制剂的进一步结构优化设计。 英文摘要: Comparative Molecular Field Analysis ( CoMFA ) and Comparative Molecular Similarity Indices Analysis (CoMSIA) were used to construct three-dimensional quantitative structure-activity relationship (3D-QSAR) models of 42 2, 4-diaminopyrimidine FAK inhibitors. The effect of template molecule, common skeleton points, minimum energy optimization parameter and molecular conformation on model optimization were evaluated. The relationship of stereo field, electrostatic field, and hydrogen bond on the activity of FAK inhibitors were analyzed. Using molecular docking, the interaction between these inhibitors and FAK protein was analyzed. The results indicated that when compound 16 was selected as the template molecule, skeleton A was used as the common skeleton point, and the minimum energy optimization parameters of charge, maximum iteration coefficient and minimum energy limit were MMFF94, 1000 and 0. 01 Kcal / mol, respectively, the model constructed was the best. The cross-validation coefficients ( q2 ) of the 3D-QSAR model constructed by CoMFA and CoMSIA were 0. 666 and 0. 736, the non cross validation coefficients ( R2 ) were 0. 990 and 0. 989, respectively, indicating good predictions. The effect of introducing substituents at different positions on the activity of FAK inhibitors was directly reflected by the obtained three-dimensional isometric views. The molecular docking analysis showed that hydrogen bonds were formed with CYS502, ASP564, and strong hydrophobic interactions were observed formed with the surrounding residues. The parameters play important roles in the construction of 3D-QSAR model. The 3D-QSAR models constructed in this study have good predictive abilities. The 3D-QSAR and molecular docking analysis provide the basis for the design, synthesis and structural optimization of 2,4-diaminopyrimidine FAK inhibitors. 查看全文查看/发表评论下载PDF阅读器 相关附件:版权转让声明书修改意见回复 -->
要找考研考博专业课真题、题库、视频?这里资源超全!在线免费阅读!
2万种考研考博电子书(题库、视频、全套资料)及历年真题,涵盖547所院校4万余个考研考博专业科目、考研公共课(政治英语数学)、40种专业硕士(金融硕士、MBA、国际商务硕士、新闻传播硕士、社会工作硕士等)、28类同等学力申硕专业、1130种经典教材。无论您是真题演练、题库刷题,还是复习教材,一个VIP会员均可满足您的需求。
相关话题/贵州医科大学 优化 中文 实验 工程

开通VIP:万种考研考证视频随便看,每本不到一分钱
547所院校考研考博1130种指定教材的千余种配套题库、视频,涵盖英语、经济、证券、金融、理工、管理、社会、财会、教育心理、中文、艺术、新闻传播、法学、医学、计算机、历史、地理、政治、哲学、体育类等28类学科,VIP会员低至128.00元!