| Title |
Rationalization of stereospecific binding of propranolol to cytochrome P450 2D6 by free energy calculations
|
|---|---|
| Published in |
European Biophysics Journal, October 2012
|
| DOI | 10.1007/s00249-012-0865-x |
| Pubmed ID | |
| Authors |
Gabor Nagy, Chris Oostenbrink |
| 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. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 6% |
| Czechia | 1 | 6% |
| Unknown | 15 | 88% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 29% |
| Student > Master | 3 | 18% |
| Student > Ph. D. Student | 2 | 12% |
| Lecturer > Senior Lecturer | 1 | 6% |
| Student > Bachelor | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 4 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 5 | 29% |
| Biochemistry, Genetics and Molecular Biology | 2 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 6% |
| Mathematics | 1 | 6% |
| Chemical Engineering | 1 | 6% |
| Other | 4 | 24% |
| Unknown | 3 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 April 2013.
All research outputs
#20,191,579
of 22,708,120 outputs
Outputs from European Biophysics Journal
#416
of 489 outputs
Outputs of similar age
#156,379
of 176,048 outputs
Outputs of similar age from European Biophysics Journal
#2
of 3 outputs
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