ReviewCancer metastasis reviews2020
Dynamically encoded reactivity of Ras enzymes: opening new frontiers for drug discovery.
Review in Cancer metastasis reviews, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Improving Protein Structure Determination by Integrating Ensemble-Driven Molecular Dynamics with Chemical Shift-Based Restraints.Journal of chemical information and modeling · 2026Article
- Conformational Dynamics and Catalytic Backups in a Hyper-thermostable Engineered Archaeal Protein Tyrosine Phosphatase.JACS Au · 2026Article
- Redefining the Limits of Functional Continuity in the Early Evolution of P-Loop NTPases.Molecular biology and evolution · 2025Article
- Structural Dynamics of Rho GTPases.Journal of molecular biology · 2025Review
- Loop dynamics and the evolution of enzyme activity.Nature reviews. Chemistry · 2023Review
- NMR-Chemical-Shift-Driven Protocol Reveals the Cofactor-Bound, Complete Structure of Dynamic Intermediates of the Catalytic Cycle of Oncogenic KRAS G12C Protein and the Significance of the MgInternational journal of molecular sciences · 2023Article
- The RNA-binding proteins hnRNP H and F regulate splicing of a MYC-dependent HRAS exon in prostate cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Dynamic regulation of RAS and RAS signaling.The Biochemical journal · 2023Article
- Discovering and Targeting Dynamic Drugging Pockets of Oncogenic Proteins: The Role of Magnesium in Conformational Changes of the G12D Mutated Kirsten Rat Sarcoma-Guanosine Diphosphate Complex.International journal of molecular sciences · 2022Article
- The Importance of MgChemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Identification of functional substates of KRas during GTP hydrolysis with enhanced sampling simulations.Physical chemistry chemical physics : PCCP · 2022Article
- Genetic regressive trajectories in colorectal cancer: A new hallmark of oligo-metastatic disease?Translational oncology · 2021Review
- Natural Products Attenuating Biosynthesis, Processing, and Activity of Ras Oncoproteins: State of the Art and Future Perspectives.Biomolecules · 2020Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Decoding molecular flexibility in order to understand and predict biological processes-applying the principles of dynamic-structure-activity relationships (DSAR)-becomes a necessity when attempting to design selective and specific inhibitors of a protein that has overlapping interaction surfaces with its upstream and downstream partners along its signaling cascade. Ras proteins are molecular switches that meet this definition perfectly. The close-lying P-loop and the highly flexible switch I and switch II regions are the site of nucleotide-, assisting-, and effector-protein binding. Oncogenic mutations that also appear in this region do not cause easily characterized overall structural changes, due partly to the inherent conformational heterogeneity and pliability of these segments. In this review, we present an overview of the results obtained using approaches targeting Ras dynamics, such as nuclear magnetic resonance (NMR) measurements and experiment-based modeling calculations (mostly molecular dynamics (MD) simulations). These methodologies were successfully used to decipher the mutant- and isoform-specific nature of certain transient states, far-lying allosteric sites, and the internal interaction networks, as well as the interconnectivity of the catalytic and membrane-binding regions. This opens new therapeutic potential: the discovered interaction hotspots present hitherto not targeted, selective sites for drug design efforts in diverse locations of the protein matrix.
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