ArticleComputational and structural biotechnology journal2020
Comparative effects of oncogenic mutations G12C, G12V, G13D, and Q61H on local conformations and dynamics of K-Ras.
Article in Computational and structural biotechnology journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- Non-coding small RNAs buffer protein interactions to prevent oncogenic aggregation: structural dampening of aberrant PPIs by RNA.RNA biology · 2026Article
- KRAS G12C and KRAS G12D respond to lipid metabolism in an allele-specific manner.Journal of lipid research · 2026Article
- Nintedanib inhibits the VEGFR-ERK signaling pathway in human KRAS-mutated cancer cells.Cell death & disease · 2026Article
- Molecular alterations in MAPK/ERK, β-Catenin/Wnt, and PI3K/mTOR pathways in adenomatoid odontogenic tumor.Journal of applied oral science : revista FOB · 2026Article
- From quiescence to hypertrophy: existing and emerging genetic targets to fine-tune myogenesis in cultivated muscle.Frontiers in bioengineering and biotechnology · 2026Review
- Theoretical study of KRAS G12C secondary mutations influencing inhibitor resistance.Biophysics and physicobiology · 2026Article
- Exploring binding and allosteric energy landscapes for the KRAS interactions with effector proteins using Markov state modeling of conformational ensembles and allosteric network modeling.Protein science : a publication of the Protein Society · 2025Review
- Elucidating Ras protein as a dual therapeutic target for inflammation and cancer: a review.Discover oncology · 2025Review
- Article
- Survival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting.Autophagy · 2025Review
- Article
- Structural Dynamics of Rho GTPases.Journal of molecular biology · 2025Review
- Exploring KRas Protein Dynamics: An Integrated Molecular Dynamics Analysis of KRas Wild and Mutant Variants.ACS omega · 2024Article
- RAS G-domains allosterically contribute to the recognition of lipid headgroups and acyl chains.The Journal of cell biology · 2024Article
- Bladder cancer biomarkers: current approaches and future directions.Frontiers in oncology · 2024Review
- Studying early structural changes in SOS1 mediated KRAS activation mechanism.Current research in structural biology · 2024Article
- Conformational plasticity and allosteric communication networks explain Shelterin protein TPP1 binding to human telomerase.Communications chemistry · 2023Article
- Allosteric Regulation of Switch-II Domain Controls KRAS Oncogenicity.Cancer research · 2023Article
- Mechanism-Based Redesign of GAP to Activate Oncogenic Ras.Journal of the American Chemical Society · 2023Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
K-Ras is the most frequently mutated protein in human cancers. However, until very recently, its oncogenic mutants were viewed as undruggable. To develop inhibitors that directly target oncogenic K-Ras mutants, we need to understand both their mutant-specific and pan-mutant dynamics and conformations. Recently, we have investigated how the most frequently observed K-Ras mutation in cancer patients, G12D, changes its local dynamics and conformations (Vatansever et al., 2019). Here, we extend our analysis to study and compare the local effects of other frequently observed oncogenic mutations, G12C, G12V, G13D and Q61H. For this purpose, we have performed Molecular Dynamics (MD) simulations of each mutant when active (GTP-bound) and inactive (GDP-bound), analyzed their trajectories, and compared how each mutant changes local residue conformations, inter-protein distance distributions, local flexibility and residue pair correlated motions. Our results reveal that in the four active oncogenic mutants we have studied, the α2 helix moves closer to the C-terminal of the α3 helix. However, P-loop mutations cause α3 helix to move away from Loop7, and only G12 mutations change the local conformational state populations of the protein. Furthermore, the motions of coupled residues are mutant-specific: G12 mutations lead to new negative correlations between residue motions, while Q61H destroys them. Overall, our findings on the local conformational states and protein dynamics of oncogenic K-Ras mutants can provide insights for both mutant-selective and pan-mutant targeted inhibition efforts.
Indexed as
Identifiers
What OpenQuestion holds
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.