Targeting flexibility: a structure-based computational study revealing allosteric HIV-1 protease inhibitors
Journal of Cheminformatics volume 6, Article number: P48 (2014)
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 . 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 . The most potent hit shows inhibition in a non-competitive mode of action.
Weisel M, Proschak E, Schneider G: Chem Cent J. 2007, 1: 7-10.1186/1752-153X-1-7.
Weisel M, Geppert T, Schneider P, Hoy B, Wessler S, Schneider G: PLoS One. 2011, 6: 3-
About this article
Cite this article
Kunze, J., Todoroff, N., Rodrigues, T. et al. Targeting flexibility: a structure-based computational study revealing allosteric HIV-1 protease inhibitors. J Cheminform 6 (Suppl 1), P48 (2014). https://doi.org/10.1186/1758-2946-6-S1-P48