会议专题

Molecular dynamics simulations of HIV-1 protease monomer: Assembly of N-terminus and C-terminus into β-sheet in water solution

HIV-1 protease (HTV-PR) consists of two identical subunits that are united together through a four-stranded antiparallel P-sheet formed of the peptide termini of each mono mer. Since the active site exists only in the dimer, a strategy that is attracting more and more attention in inhibitor design and which may overcome the serious drug resistance caused by competitive inhibitors is to block the peptide termini of the monomer, thereby interfering with formation of the active dimer. In the present work, we performed several extensive molecular dynamics (MD) simulations of the HIV-PR monomer in water to illustrate its solvated conformation and dynamics behavior. We found that the peptide termini usually assembled into fi sheet after several nanoseconds simulation, and became much less flexible. This P-sheet is stabilized by intramolecular interactions and is not easily disaggregated under the present MD simulation conditions. This transformation may be an important transi tion during the relaxing and equilibrating of the HIV-PR monomer in aqueous solution, and the terminal p-sheet may be one of the major conformations of the solvated HIV-PR monomer termini in water. This work may provide new insights into the dynamics behavior and dimerization mechanism of HIV-PR, and more significantly, offer a more rational receptor model for the design and discovery of novel dimerization inhibitors than crystalline structures.

HIV-1 protease termini conformation molecular dynamics simulations dynamics behavior dimerization inhibitor

Mao-Cai Yan Yu Sha Jian Wang Xu-Qiong Xiong Jin-Hong Ren Mao-Sheng Cheng

Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engi Key Laboratory of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engi

国际会议

第四届国际分子模拟与信息技术应用学术会议(The 4th International Conference of Molecular Simulations and Applied Informatics Technologies)

广州

英文

463-470

2008-11-01(万方平台首次上网日期,不代表论文的发表时间)