title: Molecular dynamics studies on the HIV-1 integrase catalytic domain.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0365, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Lins
authors.forename: J M
authors.initials: JM
authors.lastname: Briggs
authors.forename: T P
authors.initials: TP
authors.lastname: Straatsma
authors.forename: H A
authors.initials: HA
authors.lastname: Carlson
authors.forename: J
authors.initials: J
authors.lastname: Greenwald
authors.forename: S
authors.initials: S
authors.lastname: Choe
authors.forename: J A
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D000595:Amino Acid Sequence; D001358:Avian Sarcoma Viruses / Q000201:enzymology / Q000235:genetics; D055592:Biophysical Phenomena; D001703:Biophysics; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D019427:HIV Integrase / Q000737:chemistry* / Q000235:genetics; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008670:Metals / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013816:Thermodynamics
chemical_list: D008670:Metals; D019427:HIV Integrase