title: Identification of novel anthrax toxin countermeasures using in silico methods.
abstract: Anthrax is an acute infectious disease caused by the spore-forming, gram-positive, rod-shaped bacterium Bacillus anthracis. The anthrax toxin lethal factor (LF) is the primary anthrax toxin component responsible for cytotoxicity and host death and has been a heavily researched target for design of postexposure therapeutics in the event of a bioterror attack. Various computer-aided drug design methodologies have proven useful for pinpointing new antianthrax drug scaffolds, optimizing existing leads and probes, and elucidating key mechanisms of action. We present a selection of in silico virtual screening protocols incorporating docking and scoring, shape-based searching, and pharmacophore mapping techniques to identify and prioritize small molecules with potential biological activity against LF. We also recommend screening parameters that have been shown to increase the accuracy and reliability of these computational results.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Ting-Lan
authors.initials: TL
authors.lastname: Chiu
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Maize
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Amin
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000187:drug effects; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D019295:Computational Biology / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D014584:User-Computer Interface
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin