Katie Whalen - Exploiting Enzyme Plasticity in Virtual Screening: High Efficiency Inhibitors of Glutamate Racemase

Version 1

      Publication Details (including relevant citation   information):

      pp 9–13

      Abstract:

      Glutamate racemase is an attractive antimicrobial drug target.   Virtual  screening using a transition-state conformation of   the enzyme resulted  in the discovery of several μM   competitive inhibitors, dissimilar from  current amino   acid-like inhibitors, providing novel scaffolds for drug    discovery. The most effective of these competitive inhibitors   possesses a  very high ligand efficiency value of −0.6   kcal/mol/heavy atom, and is  effective against three   distinct glutamate racemases representing two  species of   Bacillus. The benefits of employing the transition-state   conformation of the receptor in virtual screening are discussed.

      Address (URL): http://pubs.acs.org/doi/abs/10.1021/ml900005b