ArticlePLoS computational biology2012
A preformed binding interface in the unbound ensemble of an intrinsically disordered protein: evidence from molecular simulations.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 115 citations in OpenAlex.
- Transient tertiary structure in intrinsically disordered proteins revealed by multithermal enhanced sampling.Nature communications · 2026Article
- Accurate conformational ensembles of intrinsically disordered proteins using reweighting based on NMR chemical shifts.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- Combining enhanced sampling and deep learning dimensionality reduction for the study of the heat shock protein B8 and its pathological mutant K141E.RSC advances · 2022Article
- A modular approach to map out the conformational landscapes of unbound intrinsically disordered proteins.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- NMR Provides Unique Insight into the Functional Dynamics and Interactions of Intrinsically Disordered Proteins.Chemical reviews · 2022Review
- Molecular Simulations of Intrinsically Disordered Proteins and Their Binding Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Common sequence motifs of nascent chains engage the ribosome surface and trigger factor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions.Biomolecules · 2021Review
- High resolution ensemble description of metamorphic and intrinsically disordered proteins using an efficient hybrid parallel tempering scheme.Nature communications · 2021Article
- Ubiquitin Interacting Motifs: Duality Between Structured and Disordered Motifs.Frontiers in molecular biosciences · 2021Article
- Investigating the Conformational Ensembles of Intrinsically Disordered Proteins with a Simple Physics-Based Model.The journal of physical chemistry. B · 2020Article
- Targeting Intrinsically Disordered Proteins through Dynamic Interactions.Biomolecules · 2020Review
- Sequence specificity despite intrinsic disorder: How a disease-associated Val/Met polymorphism rearranges tertiary interactions in a long disordered protein.PLoS computational biology · 2019Article
- Residual Structure Accelerates Binding of Intrinsically Disordered ACTR by Promoting Efficient Folding upon Encounter.Journal of molecular biology · 2019Article
- Studies on Molecular Dynamics of Intrinsically Disordered Proteins and Their Fuzzy Complexes: A Mini-Review.Computational and structural biotechnology journal · 2019Review
- Transition path times of coupled folding and binding reveal the formation of an encounter complex.Nature communications · 2018Article
- Force field development and simulations of intrinsically disordered proteins.Current opinion in structural biology · 2018Review
- Article
- Enhanced Sampling of Intrinsic Structural Heterogeneity of the BH3-Only Protein Binding Interface of Bcl-xL.The journal of physical chemistry. B · 2017Article
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Intrinsically disordered proteins play an important role in cellular signalling, mediated by their interactions with other biomolecules. A key question concerns the nature of their binding mechanism, and whether the bound structure is induced only by proximity to the binding partner. This is difficult to answer through experiment alone because of the very heterogeneous nature of the unbound ensemble, and the probable rapid interconversion of the various unbound structures. Here we report the most extensive set of simulations on NCBD to date: we use large-scale replica exchange molecular dynamics to explore the unbound state. An important feature of the study is the use of an atomistic force field that has been parametrised against experimental data for weakly structured peptides, together with an accurate explicit water model. Neither the force field nor the starting conformations are biased towards a particular structure. The regions of NCBD that have high helical propensity in the simulations correspond closely to helices in the 'core' unbound conformation determined by NMR, although no single member of the simulated unbound ensemble closely resembles the core conformation, or either of the two known bound conformations. We have validated the results against NMR spectroscopy and SAXS measurements, obtaining reasonable agreement. The two helices which most stabilise the binding of NCBD with ACTR are formed readily; the third helix, which is less important for binding but is involved in most of the intraprotein contacts of NCBD in the bound conformation, is formed more rarely, and tends not to coexist with the other helices. These results support a mechanism by which NCBD gains the advantages of disorder, while forming binding-competent structures in the unbound state. We obtain support for this mechanism from coarse-grained simulations of NCBD with, and without, its binding partner.
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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.