FLAP OPENING IN HIV-1 PROTEASE SIMULATED BY ACTIVATED MOLECULAR-DYNAMICS

被引：134

作者：

COLLINS, JR ^{[1
]}

BURT, SK ^{[1
]}

ERICKSON, JW ^{[1
]}

机构：

[1] NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702

来源：

NATURE STRUCTURAL BIOLOGY | 1995年 / 2卷 / 04期

关键词：

D O I：

10.1038/nsb0495-334

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have used an 'activated' molecular dynamics approach to simulate flap opening in HIV-1 protease. An initial impulse for flap opening was provided by applying harmonic constraints to non-flap residues. After an initial 'melting' phase, the two beta-hairpin structures that constitute the flaps opened to a 25 Angstrom gap within 200 ps of simulation. Analysis of backbone torsion angles suggests that flap opening is related to conformational changes at Lys 45, Met 46, Gly 52 and Phe 53. In contrast, similar molecular dynamics simulations on the M46l mutant, which is associated with drug resistance, indicates that this mutation stabilizes the flaps in a dosed conformation.

引用

页码：334 / 338

页数：5

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