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  • 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


© Kunze et al; licensee Chemistry Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.