ArticlePloS one2011
The energy landscape analysis of cancer mutations in protein kinases.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- Explainable AI reveals the allosteric blind spot in protein-ligand binding predictions.Cell reports. Physical science · 2026Article
- 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
- Integrated Framework for Probing Multimodal Protein Foundation Models with Structure-Functional Interpretability Analysis in Detection of Allosteric Binding Sites.bioRxiv : the preprint server for biology · 2026Article
- Predicting and Decoding Allosteric Binding Sites Using Protein Language Models and Structure-Based Machine Learning: An Energy Landscape-Guided Explainable AI Framework.Journal of chemical theory and computation · 2026Article
- Frustration in physiology and molecular medicine.Molecular aspects of medicine · 2025Review
- Integration of a Randomized Sequence Scanning Approach in AlphaFold2 and Local Frustration Profiling of Conformational States Enable Interpretable Atomistic Characterization of Conformational Ensembles and Detection of Hidden Allosteric States in the ABL1 Protein Kinase.Journal of chemical theory and computation · 2024Article
- Structural and functional implications of SLC13A3 and SLC9A6 mutations: an in silico approach to understanding intellectual disability.BMC neurology · 2023Article
- Defensin-based therapeutic peptide design in attenuating V30M TTR-induced Familial Amyloid Polyneuropathy.3 Biotech · 2023Article
- Deep computational phenotyping of genomic variants impacting the SET domain of KMT2C reveal molecular mechanisms for their dysfunction.Frontiers in genetics · 2023Article
- Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs.Journal of molecular biology · 2022Review
- Frustration analysis of TBK1 missense mutations reported in ALS/FTD and cancer patients.3 Biotech · 2022Article
- Evaluation of residue variability in a conformation-specific context and during evolutionary sequence reconstruction narrows drug resistance selection in Abl1 tyrosine kinase.Protein science : a publication of the Protein Society · 2022Article
- Allostery, and how to define and measure signal transduction.Biophysical chemistry · 2022Review
- Untangling Dual-Targeting Therapeutic Mechanism of Epidermal Growth Factor Receptor (EGFR) Based on Reversed Allosteric Communication.Pharmaceutics · 2021Article
- Anomalous structural dynamics of minimally frustrated residues in cardiac troponin C triggers hypertrophic cardiomyopathy.Chemical science · 2021Article
- Allosteric Regulation at the Crossroads of New Technologies: Multiscale Modeling, Networks, and Machine Learning.Frontiers in molecular biosciences · 2020Review
- Integration of Random Forest Classifiers and Deep Convolutional Neural Networks for Classification and Biomolecular Modeling of Cancer Driver Mutations.Frontiers in molecular biosciences · 2019Article
- Article
- Conformational landscape of the epidermal growth factor receptor kinase reveals a mutant specific allosteric pocket.Chemical science · 2018Article
- Elucidation of the structural stability and dynamics of heterogeneous intermediate ensembles in unfolding pathway of the N-terminal domain of TDP-43.RSC advances · 2018Article
Corrections and comments
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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 growing interest in quantifying the molecular basis of protein kinase activation and allosteric regulation by cancer mutations has fueled computational studies of allosteric signaling in protein kinases. In the present study, we combined computer simulations and the energy landscape analysis of protein kinases to characterize the interplay between oncogenic mutations and locally frustrated sites as important catalysts of allostetric kinase activation. While structurally rigid kinase core constitutes a minimally frustrated hub of the catalytic domain, locally frustrated residue clusters, whose interaction networks are not energetically optimized, are prone to dynamic modulation and could enable allosteric conformational transitions. The results of this study have shown that the energy landscape effect of oncogenic mutations may be allosteric eliciting global changes in the spatial distribution of highly frustrated residues. We have found that mutation-induced allosteric signaling may involve a dynamic coupling between structurally rigid (minimally frustrated) and plastic (locally frustrated) clusters of residues. The presented study has demonstrated that activation cancer mutations may affect the thermodynamic equilibrium between kinase states by allosterically altering the distribution of locally frustrated sites and increasing the local frustration in the inactive form, while eliminating locally frustrated sites and restoring structural rigidity of the active form. The energy landsape analysis of protein kinases and the proposed role of locally frustrated sites in activation mechanisms may have useful implications for bioinformatics-based screening and detection of functional sites critical for allosteric regulation in complex biomolecular systems.
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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.