Molecular dynamics studies on the HIV-1 integrase catalytic domain

被引:74
作者
Lins, RD
Briggs, JM
Straatsma, TP
Carlson, HA
Greenwald, J
Choe, S
McCammon, JA
机构
[1] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[2] Pacific NW Lab, Environm Mol Sci Lab, Richland, WA 99352 USA
[3] Salk Inst, San Diego, CA 92186 USA
关键词
D O I
10.1016/S0006-3495(99)77453-9
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
The HIV-I integrase, which is essential for viral replication, catalyzes the insertion of viral DNA into the host chromosome, thereby recruiting host cell machinery into making viral proteins. It represents the third main HIV enzyme target for inhibitor design, the first two being the reverse transcriptase and the protease. Two l-ns molecular dynamics simulations have been carried out on completely hydrated models of the HIV-1 integrase catalytic domain, one with no metal ions and another with one magnesium ion in the catalytic site. The simulations predict that the region of the active site that is missing in the published crystal structures has (at the time of this work) more secondary structure than previously thought. The flexibility of this region has been discussed with respect to the mechanistic function of the enzyme. The results of these simulations will be used as part of inhibitor design projects directed against the catalytic domain of the enzyme.
引用
收藏
页码:2999 / 3011
页数:13
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