Zhang Shuqun, Lin Zichun, Pu Yinglan, Zhang Yunqin, Zhang Li, Zuo Zhili
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
The Library of Yunnan Province, Kunming, China.
Comput Biol Chem. 2017 Apr;67:38-47. doi: 10.1016/j.compbiolchem.2016.12.008. Epub 2016 Dec 23.
The inhibition of β-secretase (BACE1) is currently the main pharmacological strategy available for Alzheimer's disease (AD). 2D QSAR and 3D QSAR analysis on some cyclic sulfone hydroxyethylamines inhibitors against β-secretase (IC: 0.002-2.75μM) were carried out using hologram QSAR (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) methods. The best model based on the training set was generated with a HQSAR q value of 0.693 and r value of 0.981; a CoMFA q value of 0.534 and r value of 0.913; and a CoMSIA q value of 0.512 and r value of 0.973. In order to gain further understand of the vital interactions between cyclic sulfone hydroxyethylamines and the protease, the analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the BACE1. The final QSAR models could be helpful in the design and development of novel active BACE1 inhibitors.
抑制β-分泌酶（BACE1）是目前治疗阿尔茨海默病（AD）可用的主要药理学策略。使用全息定量构效关系（HQSAR）、比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）方法，对一些针对β-分泌酶的环状砜羟乙胺抑制剂（IC：0.002 - 2.75μM）进行了二维定量构效关系（2D QSAR）和三维定量构效关系（3D QSAR）分析。基于训练集生成的最佳模型中，HQSAR的q值为0.693，r值为0.981；CoMFA的q值为0.534，r值为0.913；CoMSIA的q值为0.512，r值为0.973。为了进一步了解环状砜羟乙胺与蛋白酶之间的重要相互作用，通过将CoMFA和CoMSIA场分布与BACE1的活性位点相结合进行了分析。最终的定量构效关系模型可能有助于新型活性BACE1抑制剂的设计和开发。
