[NMR paper] Predicting and Understanding the Enzymatic Inhibition of Human Peroxiredoxin 5 by 4-Substituted Pyrocatechols Combining Funnel-Metadynamics, Solution NMR and Steady-State Kinetics.

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Predicting and Understanding the Enzymatic Inhibition of Human Peroxiredoxin 5 by 4-Substituted Pyrocatechols Combining Funnel-Metadynamics, Solution NMR and Steady-State Kinetics.

Related Articles Predicting and Understanding the Enzymatic Inhibition of Human Peroxiredoxin 5 by 4-Substituted Pyrocatechols Combining Funnel-Metadynamics, Solution NMR and Steady-State Kinetics.

Biochemistry. 2016 May 30;

Authors: Chow ML, Troussicot L, Martin M, Doumèche B, Guillière F, Lancelin JM

Abstract
Funnel-metadynamics is a kind of computational simulation used to enhance the sampling of protein-ligand binding events in solution. By characterizing the binding interaction events an estimated absolute binding free-energy can be calculated. NMR and funnel-metadynamics were used to evaluate the binding interaction of pyrocatechol derivatives (catechol, 4-methylcatechol and 4-tert-butylcatechol) to human peroxiredoxin 5. Human peroxiredoxins are peroxidases involved in cellular peroxide homeostasis. Recently, peroxiredoxins levels overexpressed or suppressed have been linked to various diseases. Here, the catechol derivatives were found to be inhibitors against human peroxiredoxin 5 through a partial mixed type non-competitive mechanism. Funnel-metadynamics provided a micro-scopic model to interpret the inhibition mechanism. Correlations were observed between the inhibition constants to the absolute binding free energy. Overall, this study showcases that funnel-metadynamics simulations could be employed as a preliminary approach to gain an in-depth understanding of potential enzyme inhibitors.


PMID: 27239955 [PubMed - as supplied by publisher]



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