title: Revealing interaction mode between HIV-1 protease and mannitol analog inhibitor.
abstract: HIV protease is a key enzyme to play a key role in the HIV-1 replication cycle and control the maturation from HIV viruses to an infectious virion. HIV-1 protease has become an important target for anti-HIV-1 drug development. Here, we used molecular dynamics simulation to study the binding mode between mannitol derivatives and HIV-1 protease. The results suggest that the most active compound (M35) has more stable hydrogen bonds and stable native contacts than the less active one (M17). These mannitol derivatives might have similar interaction mode with HIV-1 protease. Then, 3D-QSAR was used to construct quantitative structure-activity models. The cross-validated q(2)  values are found as 0.728 and 0.611 for CoMFA and CoMSIA, respectively. And the non-cross-validated r(2)  values are 0.973 and 0.950. Nine test set compounds validate the model. The results show that this model possesses better prediction ability than the previous work. This model can be used to design new chemical entities and make quantitative prediction of the bioactivities for HIV-1 protease inhibitors before resorting to in vitro and in vivo experiment.
authors.affiliation: State Key Laboratory of Microbial metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
authors.forename: Guan-Wen
authors.initials: GW
authors.lastname: Yan
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Chen
mesh_terms: D001665:Binding Sites; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D006860:Hydrogen Bonding; D008353:Mannitol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship
chemical_list: D017320:HIV Protease Inhibitors; D008353:Mannitol; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1