ArticleScientific reports2019
Oncogenic G12D mutation alters local conformations and dynamics of K-Ras.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 94 citations in OpenAlex.
- Targeted therapeutic strategies forTranslational lung cancer research · 2026Review
- Benchmarking docking and ML re-scoring screening performance for KRAS G12D in pancreatic cancer.Molecular diversity · 2026Article
- Review
- The multimerization pathway of the glucocorticoid receptor.Nucleic acids research · 2025Article
- 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
- Article
- KRAS mutated NSCLC: past, present, and future directions in a rapidly evolving landscape.The oncologist · 2025Review
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Survival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting.Autophagy · 2025Review
- Article
- Elucidating the therapeutic potential of indazole derivative bindarit against K-ras receptor: AnBiochemistry and biophysics reports · 2025Article
- Structural Dynamics of Rho GTPases.Journal of molecular biology · 2025Review
- Association between KRAS mutation and alcohol consumption in Brazilian patients with colorectal cancer.Scientific reports · 2024Article
- Insight into structural dynamics involved in activation mechanism of full length KRAS wild type and P-loop mutants.Heliyon · 2024Article
- Cracking the Codes behind Cancer Cells' Immune Evasion.International journal of molecular sciences · 2024Review
- Exploring KRas Protein Dynamics: An Integrated Molecular Dynamics Analysis of KRas Wild and Mutant Variants.ACS omega · 2024Article
- Assessing the mechanism of fast-cycling cancer-associated mutations of Rac1 small Rho GTPase.Protein science : a publication of the Protein Society · 2024Article
- Discovery of Novel Noncovalent KRAS G12D Inhibitors through Structure-Based Virtual Screening and Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2024Article
- Insights into direct KRAS inhibition strategies for cancer treatment.Future medicinal chemistry · 2024Review
- Structural perspectives on recent breakthrough efforts toward direct drugging of RAS and acquired resistance.Frontiers in oncology · 2024Review
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 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
K-Ras is the most frequently mutated oncoprotein in human cancers, and G12D is its most prevalent mutation. To understand how G12D mutation impacts K-Ras function, we need to understand how it alters the regulation of its dynamics. Here, we present local changes in K-Ras structure, conformation and dynamics upon G12D mutation, from long-timescale Molecular Dynamics simulations of active (GTP-bound) and inactive (GDP-bound) forms of wild-type and mutant K-Ras, with an integrated investigation of atomistic-level changes, local conformational shifts and correlated residue motions. Our results reveal that the local changes in K-Ras are specific to bound nucleotide (GTP or GDP), and we provide a structural basis for this. Specifically, we show that G12D mutation causes a shift in the population of local conformational states of K-Ras, especially in Switch-II (SII) and α3-helix regions, in favor of a conformation that is associated with a catalytically impaired state through structural changes; it also causes SII motions to anti-correlate with other regions. This detailed picture of G12D mutation effects on the local dynamic characteristics of both active and inactive protein helps enhance our understanding of local K-Ras dynamics, and can inform studies on the development of direct inhibitors towards the treatment of K-Ras
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.