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Molecular dynamics simulations of HIV‐1 protease monomer: Assembly of N‐terminus and C‐terminus into β‐sheet in water solution
Author(s) -
Yan MaoCai,
Sha Yu,
Wang Jian,
Xiong XuQiong,
Ren JinHong,
Cheng MaoSheng
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21539
Subject(s) - antiparallel (mathematics) , hiv 1 protease , monomer , molecular dynamics , chemistry , dimer , beta sheet , peptide , protease , biophysics , protein structure , stereochemistry , crystallography , computational chemistry , biochemistry , biology , enzyme , physics , organic chemistry , quantum mechanics , magnetic field , polymer
HIV‐1 protease (HIV‐PR) consists of two identical subunits that are united together through a four‐stranded antiparallel β‐sheet formed of the peptide termini of each monomer. 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 β‐sheet after several nanoseconds' simulation, and became much less flexible. This β‐sheet is stabilized by intramolecular interactions and is not easily disaggregated under the present MD simulation conditions. This transformation may be an important transition during the relaxing and equilibrating of the HIV‐PR monomer in aqueous solution, and the terminal β‐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. Proteins 2008. © 2007 Wiley‐Liss, Inc.