ArticleNature communications2015
Allostery through the computational microscope: cAMP activation of a canonical signalling domain.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Harnessing virtual screening and MD simulations: a multistage approach to identifying potent and nontoxic agonists for protein kinase A.Molecular diversity · 2026Article
- Markovian state models uncover casein kinase 1 dynamics that govern circadian period.Biophysical journal · 2025Article
- Unveiling the Conformational Dynamics of the Histone Tails Using Markov State Modeling.Journal of chemical theory and computation · 2025Article
- Exploring transition states of protein conformational changes via out-of-distribution detection in the hyperspherical latent space.Nature communications · 2025Article
- Tutorial on how to build non-Markovian dynamic models from molecular dynamics simulations for studying protein conformational changes.The Journal of chemical physics · 2024Article
- Purine nucleosides replace cAMP in allosteric regulation of PKA in trypanosomatid pathogens.eLife · 2024Article
- Perspectives on Computational Enzyme Modeling: From Mechanisms to Design and Drug Development.ACS omega · 2024Review
- In silico discovery of potential PPI inhibitors for anti-lung cancer activity by targeting the CCND1-CDK4 complex via the P21 inhibition mechanism.Frontiers in chemistry · 2024Article
- Active and machine learning-enhanced discovery of new FGFR3 inhibitor, Rhapontin, through virtual screening of receptor structures and anti-cancer activity assessment.Frontiers in molecular biosciences · 2024Article
- Integrative generalized master equation: A method to study long-timescale biomolecular dynamics via the integrals of memory kernels.The Journal of chemical physics · 2023Article
- An Efficient Path Classification Algorithm Based on Variational Autoencoder to Identify Metastable Path Channels for Complex Conformational Changes.Journal of chemical theory and computation · 2023Article
- Critical role of backbone coordination in the mRNA recognition by RNA induced silencing complex.Communications biology · 2021Article
- Markov State Models to Study the Functional Dynamics of Proteins in the Wake of Machine Learning.JACS Au · 2021Review
- Probing allosteric regulations with coevolution-driven molecular simulations.Science advances · 2021Article
- Unsupervised Learning Methods for Molecular Simulation Data.Chemical reviews · 2021Article
- Temperature-dependent kinetic pathways of heterogeneous ice nucleation competing between classical and non-classical nucleation.Nature communications · 2021Article
- Role of bacterial RNA polymerase gate opening dynamics in DNA loading and antibiotics inhibition elucidated by quasi-Markov State Model.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Incorporation of sensing modalities into de novo designed fluorescence-activating proteins.Nature communications · 2021Article
- Deciphering the Allosteric Process of theThe journal of physical chemistry. B · 2020Article
- Allosteric Regulation at the Crossroads of New Technologies: Multiscale Modeling, Networks, and Machine Learning.Frontiers in molecular biosciences · 2020Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Ligand-induced protein allostery plays a central role in modulating cellular signalling pathways. Here using the conserved cyclic nucleotide-binding domain of protein kinase A's (PKA) regulatory subunit as a prototype signalling unit, we combine long-timescale, all-atom molecular dynamics simulations with Markov state models to elucidate the conformational ensembles of PKA's cyclic nucleotide-binding domain A for the cAMP-free (apo) and cAMP-bound states. We find that both systems exhibit shallow free-energy landscapes that link functional states through multiple transition pathways. This observation suggests conformational selection as the general mechanism of allostery in this canonical signalling domain. Further, we expose the propagation of the allosteric signal through key structural motifs in the cyclic nucleotide-binding domain and explore the role of kinetics in its function. Our approach integrates disparate lines of experimental data into one cohesive framework to understand structure, dynamics and function in complex biological systems.
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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.