ArticleEuropean biophysics journal : EBJ2012
Rationalization of stereospecific binding of propranolol to cytochrome P450 2D6 by free energy calculations.
Article in European biophysics journal : EBJ, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- Free-energy calculations of residue mutations in a tripeptide using various methods to overcome inefficient sampling.Journal of computational chemistry · 2016Article
- Predicting drug metabolism: experiment and/or computation?Nature reviews. Drug discovery · 2015Review
- Entropic and enthalpic contributions to stereospecific ligand binding from enhanced sampling methods.Journal of chemical information and modeling · 2014Article
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2 authors at 1 institution in 1 country.
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Abstract
Cytochrome P450 2D6 is a major drug-metabolising enzyme with a wide substrate range. A single-point mutation introduced in this enzyme induces stereoselective binding of R and S-propranolol whereas the wild type has no preference. The system has previously been studied both experimentally and computationally (de Graaf et al. in Eur Biophys J 36:589-599, 2007a). The in silico study reported hysteresis and significant deviations from closure of thermodynamic cycles, probably because of lack of sampling. Here, we focus on the effect of prolonged simulation time and enhanced sampling methods, such as Hamiltonian replica exchange, to reduce these problems and to improve the precision of free energy calculations. Finally we rationalize the results at a molecular level and compare data with experimental findings and previously estimated free energies.
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