ArticlePloS one2013
Computational analysis of KRAS mutations: implications for different effects on the KRAS p.G12D and p.G13D mutations.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- KRAS codon 12 and 13 mutations in relation to disease-free survival in BRAF-wild-type stage III colon cancers from an adjuvant chemotherapy trial (N0147 alliance).Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Predictive and prognostic analysis of PIK3CA mutation in stage III colon cancer intergroup trial.Journal of the National Cancer Institute · 2013Trial
- Review
- Selenium Nanoparticles Selectively Target KRAS G13D to Inhibit Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Benchmarking docking and ML re-scoring screening performance for KRAS G12D in pancreatic cancer.Molecular diversity · 2026Article
- 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
- Article
- Mortality Outcome Associated with SpecificDiagnostics (Basel, Switzerland) · 2025Article
- Insight into structural dynamics involved in activation mechanism of full length KRAS wild type and P-loop mutants.Heliyon · 2024Article
- Mediating kinase activity in Ras-mutant cancer: potential for an individualised approach?Frontiers in pharmacology · 2024Review
- Studying early structural changes in SOS1 mediated KRAS activation mechanism.Current research in structural biology · 2024Article
- YB-1 activating cascades as potential targets in KRAS-mutated tumors.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Review
- 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
- Computational Analysis of Deleterious SNPs inFrontiers in genetics · 2022Article
- Oncogenic KRAS G12D mutation promotes dimerization through a second, phosphatidylserine-dependent interface: a model for KRAS oligomerization.Chemical science · 2021Article
- Analysis of RAS gene mutations in cytogenetically normal de novo acute myeloid leukemia patients reveals some novel alterations.Saudi journal of biological sciences · 2021Article
- My personal mutanome: a computational genomic medicine platform for searching network perturbing alleles linking genotype to phenotype.Genome biology · 2021Article
- Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe issue of whether patients diagnosed with metastatic colorectal cancer who harbor KRAS codon 13 mutations could benefit from the addition of anti-epidermal growth factor receptor therapy remains under debate. The aim of the current study was to perform computational analysis to investigate the structural implications of the underlying mutations caused by c.38G>A (p.G13D) on protein conformation.
methodsMolecular dynamics (MD) simulations were performed to understand the plausible structural and dynamical implications caused by c.35G>A (p.G12D) and c.38G>A (p.G13D). The potential of mean force (PMF) simulations were carried out to determine the free energy profiles of the binding processes of GTP interacting with wild-type (WT) KRAS and its mutants (MT).
resultsUsing MD simulations, we observed that the root mean square deviation (RMSD) increased as a function of time for the MT c.35G>A (p.G12D) and MT c.38G>A (p.G13D) when compared with the WT. We also observed that the GTP-binding pocket in the c.35G>A (p.G12D) mutant is more open than that of the WT and the c.38G>A (p.G13D) proteins. Intriguingly, the analysis of atomic fluctuations and free energy profiles revealed that the mutation of c.35G>A (p.G12D) may induce additional fluctuations in the sensitive sites (P-loop, switch I and II regions). Such fluctuations may promote instability in these protein regions and hamper GTP binding.
conclusionsTaken together with the results obtained from MD and PMF simulations, the present findings implicate fluctuations at the sensitive sites (P-loop, switch I and II regions). Our findings revealed that KRAS mutations in codon 13 have similar behavior as KRAS WT. To gain a better insight into why patients with metastatic colorectal cancer (mCRC) and the KRAS c.38G>A (p.G13D) mutation appear to benefit from anti-EGFR therapy, the role of the KRAS c.38G>A (p.G13D) mutation in mCRC needs to be further investigated.
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