title: Computational predictions of corroles as a class of Hsp90 inhibitors.
abstract: Corroles have been shown experimentally to cause cell cycle arrest, and there is some evidence that this might be attributed to an inhibitory effect of corroles on Heat shock protein 90 (Hsp90), which is known to play a vital role in cancer cell proliferation. In this study, we used molecular dynamics to examine the interaction of gallium corroles with Hsp90, and found that they can bind preferentially to the ATP-binding N-terminal site. We also found that structural variations of the corrole ring can influence the binding energies and affinities of the corrole to Hsp90. We predict that both the bis-carboxylated corrole (4-Ga) and a proposed 3,17-bis-sulfonated corrole (7-Ga) are promising alternatives to Ga(III) 5,10,15-tris(pentafluorophenyl)-2,17-bis(sulfonic acid)-corrole (1-Ga) as anti-cancer agents.
authors.affiliation: Materials and Process Simulation Center, California Institute of Technology, Pasadena, California 91125, USA. wag@wag.caltech.edu.
authors.forename: Ruijie D
authors.initials: RD
authors.lastname: Teo
authors.forename: Sijia S
authors.initials: SS
authors.lastname: Dong
authors.forename: Zeev
authors.initials: Z
authors.lastname: Gross
authors.forename: Harry B
authors.initials: HB
authors.lastname: Gray
authors.forename: William A
authors.initials: WA
authors.lastname: Goddard
mesh_terms: D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology; D003198:Computer Simulation; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology; D062105:Molecular Docking Simulation; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D008024:Ligands; D018942:Macrolides; D011166:Porphyrins; C431863:corrole; C035359:monorden; C001277:geldanamycin