Molecular Dynamics Studies on the HIV-1 Integrase Catalytic Domain

Journal Article · Wed Jun 30 04:00:00 EDT 1999 · Biophysical Journal, 76(6):2999-3011

DOI:https://doi.org/10.1016/S0006-3495(99)77453-9· OSTI ID:15005632

Lins, Roberto D; Briggs, J M; Straatsma, TP; Carlson, Heather A; Greenwald, Jason; Choe, Senyon; Mccammon, Andy

The HIV-1 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 1-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.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC06-76RL01830
• OSTI ID: 15005632
• Report Number(s): PNNL-SA-30303; KP1303000
• Journal Information: Biophysical Journal, 76(6):2999-3011, Journal Name: Biophysical Journal, 76(6):2999-3011 Journal Issue: 6 Vol. 76
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
DESIGN
DNA
ENZYMES
FLEXIBILITY
MACHINERY
MAGNESIUM IONS
PROTEINS
TARGETS