ArticlePLoS computational biology2017
Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration.
Article in PLoS computational biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Exploring PROTAC Cooperativity with Coarse-Grained Alchemical Methods.The journal of physical chemistry. B · 2023Article
- Elucidating activation and deactivation dynamics of VEGFR-2 transmembrane domain with coarse-grained molecular dynamics simulations.PloS one · 2023Article
- Multiscale modelling of claudin-based assemblies: A magnifying glass for novel structures of biological interfaces.Computational and structural biotechnology journal · 2022Review
- Coordination of -1 programmed ribosomal frameshifting by transcript and nascent chain features revealed by deep mutational scanning.Nucleic acids research · 2021Article
- Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes.International journal of molecular sciences · 2021Review
- How does Sec63 affect the conformation of Sec61 in yeast?PLoS computational biology · 2021Article
- Article
- Co-translational insertion and topogenesis of bacterial membrane proteins monitored in real time.The EMBO journal · 2020Article
- Cotranslational folding stimulates programmed ribosomal frameshifting in the alphavirus structural polyprotein.The Journal of biological chemistry · 2020Article
- Dynamics of Co-translational Membrane Protein Integration and Translocation via the Sec Translocon.Journal of the American Chemical Society · 2020Review
- Translational Control by Ribosome Pausing in Bacteria: How a Non-uniform Pace of Translation Affects Protein Production and Folding.Frontiers in microbiology · 2020Review
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- Forces on Nascent Polypeptides during Membrane Insertion and Translocation via the Sec Translocon.Biophysical journal · 2018Article
- Thermotropic Liquid Crystal-Assisted Chemical and Biological Sensors.Materials (Basel, Switzerland) · 2017Review
- Molecular simulations of cellular processes.Biophysical reviews · 2017Review
- Improving membrane protein expression by optimizing integration efficiency.The Journal of biological chemistry · 2017Article
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Authors and funding
4 authors.
Funding
Abstract
We present a coarse-grained simulation model that is capable of simulating the minute-timescale dynamics of protein translocation and membrane integration via the Sec translocon, while retaining sufficient chemical and structural detail to capture many of the sequence-specific interactions that drive these processes. The model includes accurate geometric representations of the ribosome and Sec translocon, obtained directly from experimental structures, and interactions parameterized from nearly 200 μs of residue-based coarse-grained molecular dynamics simulations. A protocol for mapping amino-acid sequences to coarse-grained beads enables the direct simulation of trajectories for the co-translational insertion of arbitrary polypeptide sequences into the Sec translocon. The model reproduces experimentally observed features of membrane protein integration, including the efficiency with which polypeptide domains integrate into the membrane, the variation in integration efficiency upon single amino-acid mutations, and the orientation of transmembrane domains. The central advantage of the model is that it connects sequence-level protein features to biological observables and timescales, enabling direct simulation for the mechanistic analysis of co-translational integration and for the engineering of membrane proteins with enhanced membrane integration efficiency.
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