Differences in conformational dynamics between Plasmodium falciparum and human Hsp90 orthologues enable the structure-based discovery of pathogen-selective inhibitors.

@article{Wang2014DifferencesIC,
  title={Differences in conformational dynamics between Plasmodium falciparum and human Hsp90 orthologues enable the structure-based discovery of pathogen-selective inhibitors.},
  author={Tai Wang and William H. Bisson and Pascal M{\"a}ser and Leonardo Scapozza and Didier Picard},
  journal={Journal of medicinal chemistry},
  year={2014},
  volume={57 6},
  pages={2524-35}
}
The high sequence conservation of druggable pockets of closely related proteins can make it challenging to develop selective inhibitors. We designed a new drug discovery approach that exploits both the static and dynamic differences of two orthologues. We applied it, as a proof of concept, to identify compounds that discriminate between the molecular… CONTINUE READING