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

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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.


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    Weisel M, Proschak E, Schneider G: Chem Cent J. 2007, 1: 7-10.1186/1752-153X-1-7.

  2. 2.

    Weisel M, Geppert T, Schneider P, Hoy B, Wessler S, Schneider G: PLoS One. 2011, 6: 3-

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Correspondence to Jens Kunze.

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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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