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  • Poster presentation
  • Open Access

Targeting flexibility: a structure-based computational study revealing allosteric HIV-1 protease inhibitors

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Journal of Cheminformatics20146 (Suppl 1) :P48

  • Published:


  • Virtual Screening
  • Hinge Region
  • Pharmacophore Model
  • Surface Cavity
  • Compound Library

We present the discovery of innovative low molecular weight inhibitors against human immunodeficiency virus 1 (HIV-1) protease. Structure-based virtual screening focused on potential allosteric surface cavities revealed these compounds [1]. To identify and prioritize such cavities we performed a molecular dynamics simulation were we concentrated on flexible and transient potential binding sites. For several time-points of the simulation we computed receptor-derived pharmacophore models in the so-called hinge region ('Exo site') and screened a large screening compound library [2]. The most potent hit shows inhibition in a non-competitive mode of action.

Authors’ Affiliations

Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland


  1. Weisel M, Proschak E, Schneider G: Chem Cent J. 2007, 1: 7-10.1186/1752-153X-1-7.View ArticleGoogle Scholar
  2. Weisel M, Geppert T, Schneider P, Hoy B, Wessler S, Schneider G: PLoS One. 2011, 6: 3-Google Scholar