ArticleProceedings of the National Academy of Sciences of the United States of America2016
Dynamical network of residue-residue contacts reveals coupled allosteric effects in recognition, catalysis, and mutation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed.
- Network analysis of correlated conformational dynamics across the evolution of influenza A virus NS1.bioRxiv : the preprint server for biology · 2026Article
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- N-terminal processing unlocks global dynamics for substrate engagement in Spl proteases.Science advances · 2026Article
- Alanine Rewires the Communication Pathways Established During the Allosteric Activation of Liver Pyruvate Kinase by Fructose Bisphosphate.Journal of chemical information and modeling · 2026Article
- Mechanistic and Molecular Dynamics Studies Reveal that Increased Loop 3 Mobility Alters Substrate Capture in an NADH:Quinone Oxidoreductase.Biochemistry · 2026Article
- Network reorganization of a cold-adapted β-glucosidase couples conformational flexibility to catalytic efficiency under low-temperature conditions.Frontiers in microbiology · 2026Article
- Untangling the Complexity of Binding Across Biomolecular Interfaces with Interaction Network Models.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Structural determinants of non-covalent PPARγ inverse agonism and their therapeutic implications.Nature communications · 2025Article
- A protein dynamics-based deep learning model enhances predictions of fitness and epistasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Uncovering the Role of Distal Regions in PDK1 Allosteric Activation.ACS bio & med chem Au · 2025Article
- Evolutionary rewiring of the dynamic network underpinning allosteric epistasis in NS1 of the influenza A virus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Node features of chromosome structure networks and their connections to genome annotation.Computational and structural biotechnology journal · 2024Article
- BaNDyT: Bayesian Network modeling of molecular Dynamics Trajectories.bioRxiv : the preprint server for biology · 2024Article
- Bayesian network models identify cooperative GPCR:G protein interactions that contribute to G protein coupling.The Journal of biological chemistry · 2024Article
- Article
- High-fidelity, hyper-accurate, and evolved mutants rewire atomic-level communication in CRISPR-Cas9.Science advances · 2024Article
- Modulation of Allostery with Multiple Mechanisms by Hotspot Mutations in TetR.Journal of the American Chemical Society · 2024Article
- Unveiling the RNA-mediated allosteric activation discloses functional hotspots in CRISPR-Cas13a.Nucleic acids research · 2024Article
- New design strategies for ultra-specific CRISPR-Cas13a-based RNA detection with single-nucleotide mismatch sensitivity.Nucleic acids research · 2024Article
- Alternate conformations found in protein structures implies biological functions: A case study using cyclophilin A.Current research in structural biology · 2024Article
30 more citing papers are in PubMed but not listed here.
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4 authors.
Funding
Abstract
Detailed understanding of how conformational dynamics orchestrates function in allosteric regulation of recognition and catalysis remains ambiguous. Here, we simulate CypA using multiple-microsecond-long atomistic molecular dynamics in explicit solvent and carry out NMR experiments. We analyze a large amount of time-dependent multidimensional data with a coarse-grained approach and map key dynamical features within individual macrostates by defining dynamics in terms of residue-residue contacts. The effects of substrate binding are observed to be largely sensed at a location over 15 Å from the active site, implying its importance in allostery. Using NMR experiments, we confirm that a dynamic cluster of residues in this distal region is directly coupled to the active site. Furthermore, the dynamical network of interresidue contacts is found to be coupled and temporally dispersed, ranging over 4 to 5 orders of magnitude. Finally, using network centrality measures we demonstrate the changes in the communication network, connectivity, and influence of CypA residues upon substrate binding, mutation, and during catalysis. We identify key residues that potentially act as a bottleneck in the communication flow through the distinct regions in CypA and, therefore, as targets for future mutational studies. Mapping these dynamical features and the coupling of dynamics to function has crucial ramifications in understanding allosteric regulation in enzymes and proteins, in general.
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