Statistical analysis, optimization, and prioritization of virtual screening parameters for zinc enzymes including the anthrax toxin lethal factor.

ABSTRACT: The anthrax toxin lethal factor (LF) and matrix metalloproteinase-3 (MMP-3, stromelysin-1) are popular zinc metalloenzyme drug targets, with LF primarily responsible for anthrax-related toxicity and host death, while MMP-3 is involved in cancer- and rheumatic disease-related tissue remodeling. A number of in silico screening techniques, most notably docking and scoring, have proven useful for identifying new potential drug scaffolds targeting LF and MMP-3, as well as for optimizing lead compounds and investigating mechanisms of action. However, virtual screening outcomes can vary significantly depending on the specific docking parameters chosen, and systematic statistical significance analyses are needed to prioritize key parameters for screening small molecules against these zinc systems.

SUBMITTER: Maize KM 

PROVIDER: S-EPMC4631255 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature