Disruption of intrinsic motions as a mechanism for enzyme inhibition.

ABSTRACT: Clostridium difficile (C. diff) is one of the most common and most severe hospital-acquired infections; its consequences range from lengthened hospital stay to outright lethality. C. diff causes cellular damage through the action of two large toxins TcdA and TcdB. Recently, there has been increased effort toward developing antitoxin therapies, rather than antibacterial treatments, in hopes of mitigating the acquisition of drug resistance. To date, no analysis of the recognition mechanism of TcdA or TcdB has been attempted. Here, we use small molecule flexible docking followed by unbiased molecular dynamics to obtain a more detailed perspective on how inhibitory peptides, exemplified by two species HQSPWHH and EGWHAHT function. Using principal component analysis and generalized masked Delau

SUBMITTER: Swett RJ 

PROVIDER: S-EPMC3714872 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature