ArticlePLoS computational biology2011
Computational modeling of allosteric communication reveals organizing principles of mutation-induced signaling in ABL and EGFR kinases.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 80 citations in OpenAlex.
- Decoding the allosteric grammar of protein kinases: A dual-stream framework integrating protein language models and energy landscape frustration analysis.Protein science : a publication of the Protein Society · 2026Article
- Integrative structural and dynamics studies of epidermal growth factor receptor (EGFR).Experimental & molecular medicine · 2026Review
- Role of gut microbiota metabolites against vein graft restenosis: insights from network pharmacology, molecular docking and molecular dynamic simulation.BMC medical genomics · 2025Article
- Distinct Allosteric Networks in CDK4 and CDK6 in the Cell Cycle and in Drug Resistance.Journal of molecular biology · 2025Article
- Drug resistance and tumor heterogeneity: cells and ensembles.Biophysical reviews · 2025Review
- Mean-Field Coupling Between Local Interactions in Proteins in Relation to Chirality, Secondary, and Supersecondary Structure Formation, and Allostery.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Probing conformational landscapes and mechanisms of allosteric communication in the functional states of the ABL kinase domain using multiscale simulations and network-based mutational profiling of allosteric residue potentials.The Journal of chemical physics · 2022Article
- Origin of Correlations between Local Conformational States of Consecutive Amino Acid Residues and Their Role in Shaping Protein Structures and in Allostery.The journal of physical chemistry. B · 2022Article
- TYROSINE KINASES: COMPLEX MOLECULAR SYSTEMS CHALLENGING COMPUTATIONAL METHODOLOGIES.The European physical journal. B · 2021Article
- Genotype-determined EGFR-RTK heterodimerization and its effects on drug resistance in lung Cancer treatment revealed by molecular dynamics simulations.BMC molecular and cell biology · 2021Article
- Congenital myasthenic syndrome due to mutations in MUSK suggests that the level of MuSK phosphorylation is crucial for governing synaptic structure.Human mutation · 2020Article
- Allosteric Regulation at the Crossroads of New Technologies: Multiscale Modeling, Networks, and Machine Learning.Frontiers in molecular biosciences · 2020Review
- Review
- Allosteric Communication Networks in Proteins Revealed through Pocket Crosstalk Analysis.ACS central science · 2017Article
- Design of Elastic Networks with Evolutionary Optimized Long-Range Communication as Mechanical Models of Allosteric Proteins.Biophysical journal · 2017Article
- PBxplore: a tool to analyze local protein structure and deformability with Protein Blocks.PeerJ · 2017Article
- Discovery of Novel Allosteric Eg5 Inhibitors Through Structure-Based Virtual Screening.Chemical biology & drug design · 2016Article
- Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell.Chemical reviews · 2016Review
- Dissecting protein architecture with communication blocks and communicating segment pairs.BMC bioinformatics · 2016Article
- Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emerging structural information about allosteric kinase complexes and the growing number of allosteric inhibitors call for a systematic strategy to delineate and classify mechanisms of allosteric regulation and long-range communication that control kinase activity. In this work, we have investigated mechanistic aspects of long-range communications in ABL and EGFR kinases based on the results of multiscale simulations of regulatory complexes and computational modeling of signal propagation in proteins. These approaches have been systematically employed to elucidate organizing molecular principles of allosteric signaling in the ABL and EGFR multi-domain regulatory complexes and analyze allosteric signatures of the gate-keeper cancer mutations. We have presented evidence that mechanisms of allosteric activation may have universally evolved in the ABL and EGFR regulatory complexes as a product of a functional cross-talk between the organizing αF-helix and conformationally adaptive αI-helix and αC-helix. These structural elements form a dynamic network of efficiently communicated clusters that may control the long-range interdomain coupling and allosteric activation. The results of this study have unveiled a unifying effect of the gate-keeper cancer mutations as catalysts of kinase activation, leading to the enhanced long-range communication among allosterically coupled segments and stabilization of the active kinase form. The results of this study can reconcile recent experimental studies of allosteric inhibition and long-range cooperativity between binding sites in protein kinases. The presented study offers a novel molecular insight into mechanistic aspects of allosteric kinase signaling and provides a quantitative picture of activation mechanisms in protein kinases at the atomic level.
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