ArticlePLoS computational biology2014
A multiscale approach to modelling drug metabolism by membrane-bound cytochrome P450 enzymes.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed.
- Methods for the establishment of enzymatic mechanisms - from QM to ML.Chemical science · 2026Review
- Oxygen-Dependent Light-Induced Lipid Membrane Perturbation by TLD1433 as a Potential Contributor to Phototoxicity.Inorganic chemistry · 2026Article
- The Nature of Nanodisc Lipids Influences Fragment-Based Drug Discovery Results.Chemical biology & drug design · 2025Article
- Equilibrium landscape of ingress/egress channels and gating residues of the Cytochrome P450 3A4.PloS one · 2024Article
- Reliably assessing the electronic structure of cytochrome P450 on today's classical computers and tomorrow's quantum computers.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Machine learning-driven identification of drugs inhibiting cytochrome P450 2C9.PLoS computational biology · 2022Article
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- From System Modeling to System Analysis: The Impact of Resolution Level and Resolution Distribution in the Computer-Aided Investigation of Biomolecules.Frontiers in molecular biosciences · 2021Review
- CYP2J2 Molecular Recognition: A New Axis for Therapeutic Design.Pharmacology & therapeutics · 2020Review
- The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics.Scientific reports · 2020Article
- Article
- Molecular Dynamics Simulation Framework to Probe the Binding Hypothesis of CYP3A4 Inhibitors.International journal of molecular sciences · 2019Article
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Prediction of Ligand Transport along Hydrophobic Enzyme Nanochannels.Computational and structural biotechnology journal · 2019Article
- Multiscale Methods in Drug Design Bridge Chemical and Biological Complexity in the Search for Cures.Nature reviews. Chemistry · 2018Article
- Membrane-embedded substrate recognition by cytochrome P450 3A4.The Journal of biological chemistry · 2018Article
- Systems biology of cellular membranes: a convergence with biophysics.Wiley interdisciplinary reviews. Systems biology and medicine · 2017Review
- Atomistic modelling of scattering data in the Collaborative Computational Project for Small Angle Scattering (CCP-SAS).Journal of applied crystallography · 2016Article
- Lipid molecules can induce an opening of membrane-facing tunnels in cytochrome P450 1A2.Physical chemistry chemical physics : PCCP · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Cytochrome P450 enzymes are found in all life forms. P450s play an important role in drug metabolism, and have potential uses as biocatalysts. Human P450s are membrane-bound proteins. However, the interactions between P450s and their membrane environment are not well-understood. To date, all P450 crystal structures have been obtained from engineered proteins, from which the transmembrane helix was absent. A significant number of computational studies have been performed on P450s, but the majority of these have been performed on the solubilised forms of P450s. Here we present a multiscale approach for modelling P450s, spanning from coarse-grained and atomistic molecular dynamics simulations to reaction modelling using hybrid quantum mechanics/molecular mechanics (QM/MM) methods. To our knowledge, this is the first application of such an integrated multiscale approach to modelling of a membrane-bound enzyme. We have applied this protocol to a key human P450 involved in drug metabolism: CYP3A4. A biologically realistic model of CYP3A4, complete with its transmembrane helix and a membrane, has been constructed and characterised. The dynamics of this complex have been studied, and the oxidation of the anticoagulant R-warfarin has been modelled in the active site. Calculations have also been performed on the soluble form of the enzyme in aqueous solution. Important differences are observed between the membrane and solution systems, most notably for the gating residues and channels that control access to the active site. The protocol that we describe here is applicable to other membrane-bound enzymes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.