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The maturation of HIV‐1 protease precursor studied by discrete molecular dynamics
Author(s) -
Kimura Sachie,
Caldarini Martina,
Broglia Ricardo A.,
Dokholyan Nikolay V.,
Tiana Guido
Publication year - 2014
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.24440
Subject(s) - protease , dynamics (music) , human immunodeficiency virus (hiv) , hiv 1 protease , molecular dynamics , chemistry , mathematics , virology , biology , physics , computational chemistry , biochemistry , enzyme , acoustics
The equilibrium properties of a HIV‐1‐protease precursor are studied by means of an efficient molecular dynamics scheme, which allows for the simulation of the folding of the protein monomers and their dimerization into an active form and compare them with those of the mature protein. The results of the model provide, with atomic detail, an overall account of several experimental findings, including the NMR conformation of the mature dimer, the calorimetric properties of the system, the effects of the precursor tail on the dimerization constant, the secondary chemical shifts of the monomer, and the paramagnetic relaxation enhancement data associated with the conformations of the precursor. It is found that although the mature protein can dimerize in a unique, single way, the precursor populates several dimeric conformations in which monomers are always native‐like, but their binding can be non‐native. Proteins 2014; 82:633–639. © 2013 Wiley Periodicals, Inc.