Molecular modeling studies of human immunodeficiency virus type 1 protease inhibitors using three-dimensional quantitative structure-activity relationship, virtual screening, and docking simulations

作者：Tong, Jianbo^*; Zhan, Pei; Bai, Min; Yao, Tuanli

来源：Journal of Chemometrics, 2016, 30(9): 523-536.

DOI：10.1002/cem.2809

• 3D-QSAR
• protease (PR) inhibitors
• RASMS
• Topomer CoMFA
• molecular docking

In this paper, two 3-dimensional quantitative structure-activity relationship models for 60 human immunodeficiency virus (HIV)-1 protease inhibitors were established using random sampling analysis on molecular surface and translocation comparative molecular field vector analysis (Topomer CoMFA). The non-cross-validation (r(2)), cross-validation (q(2)), correlation coefficient of external validation (Q(ext)(2)), and F of 2 models were 0.94, 0.80, 0.79, and 198.84 and 0.94, 0.72, 0.75, and 208.53, respectively. The results indicated that 2 models were reasonable and had good prediction ability. Topomer Search was used to search R groups in the ZINC database, 20 new compounds were designed, and the Topomer CoMFA model was used to predicate the biological activity. The results showed that 18 new compounds were more active than the template molecule. So the Topomer Search is effective in screening and can guide the design of new HIV/AIDS drugs. The mechanism of action was studied by molecular docking, and it showed that the protease inhibitors and Ile50, Asp25, and Arg8 sites of HIV-1 protease have interactions. These results have provided an insight for the design of new potent inhibitors of HIV-1 protease. @@@ Two 3D-QSAR models for 60 HIV-1 protease inhibitors were established using RASMS and the Topomer CoMFA method. Twenty new inhibitors were designed using Topomer Search. The binding environment between PR inhibitors and receptor was explored by molecular docking.

• 出版日期2016-9
• 单位陕西科技大学