ArticlePloS one2012
Investigation of indazole unbinding pathways in CYP2E1 by molecular dynamics simulations.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.
What it found
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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
8 citing papers in PubMed, 38 citations in OpenAlex.
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Tryptophan-75 Is a Low-Energy Channel-Gating Residue that Facilitates Substrate Egress/Access in Cytochrome P450 2D6.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Four Major Channels Detected in the Cytochrome P450 3A4: A Step toward Understanding Its Multispecificity.International journal of molecular sciences · 2019Article
- Molecular basis of P450 OleTJournal of computer-aided molecular design · 2017Article
- Ligand tunnels in T. brucei and human CYP51: Insights for parasite-specific drug design.Biochimica et biophysica acta · 2016Article
- Structural basis for cooperative binding of azoles to CYP2E1 as interpreted through guided molecular dynamics simulations.Journal of molecular graphics & modelling · 2015Article
- Including ligand-induced protein flexibility into protein tunnel prediction.Journal of computational chemistry · 2014Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human microsomal cytochrome P450 2E1 (CYP2E1) can oxidize not only low molecular weight xenobiotic compounds such as ethanol, but also many endogenous fatty acids. The crystal structure of CYP2E1 in complex with indazole reveals that the active site is deeply buried into the protein center. Thus, the unbinding pathways and associated unbinding mechanisms remain elusive. In this study, random acceleration molecular dynamics simulations combined with steered molecular dynamics and potential of mean force calculations were performed to identify the possible unbinding pathways in CYP2E1. The results show that channel 2c and 2a are most likely the unbinding channels of CYP2E1. The former channel is located between helices G and I and the B-C loop, and the latter resides between the region formed by the F-G loop, the B-C loop and the β1 sheet. Phe298 and Phe478 act as the gate keeper during indazole unbinding along channel 2c and 2a, respectively. Previous site-directed mutagenesis experiments also supported these findings.
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