title: Discovery of a novel binding trench in HIV integrase.
abstract: Docking of the 5CITEP inhibitor to snapshots of a 2 ns HIV-1 integrase MD trajectory indicated a previously uncharacterized trench adjacent to the active site that intermittently opens. Further docking studies of novel ligands with the potential to bind to both regions showed greater selective affinity when able to bind to the trench. Our ranking of ligands is open to experimental testing, and our approach suggests a new target for HIV-1 therapeutics.
authors.affiliation: Department of Pharmacology, Howard Hughes Medical Institute, University of California-San Diego, La Jolla, CA 92093-0365, USA.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Schames
authors.forename: Richard H
authors.initials: RH
authors.lastname: Henchman
authors.forename: Jay S
authors.initials: JS
authors.lastname: Siegel
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Sotriffer
authors.forename: Haihong
authors.initials: H
authors.lastname: Ni
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D007211:Indoles / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009281:Naphthalenes / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry
chemical_list: C400757:1-(5-chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazol-5-yl)propenone; D007211:Indoles; D008024:Ligands; D009281:Naphthalenes; D013777:Tetrazoles; D019427:HIV Integrase