ArticleBiophysical journal2020
The Plasma Membrane as a Competitive Inhibitor and Positive Allosteric Modulator of KRas4B Signaling.
Article in Biophysical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Regulation of Membrane Association and Downstream Effector Interaction of K-Ras by Its Hypervariable Region.Membranes · 2026Article
- KRAS G12C and KRAS G12D respond to lipid metabolism in an allele-specific manner.Journal of lipid research · 2026Article
- Rheb membrane orientation dynamics and functional consequences elucidated by molecular simulations, single-molecule-FRET and signaling assays.bioRxiv : the preprint server for biology · 2026Article
- Dynamics and lipid membrane coupling of the RAS-RAF complex revealed via multiscale simulations.Biophysical journal · 2026Article
- RAS-membrane interaction and oligomerization: there is more than meets the eye.Biochemical Society transactions · 2025Review
- Article
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- From disorder comes function: Regulation of small GTPase function by intrinsically disordered lipidated membrane anchor.Current opinion in structural biology · 2024Review
- RAS G-domains allosterically contribute to the recognition of lipid headgroups and acyl chains.The Journal of cell biology · 2024Article
- Conserved allosteric perturbation of the GTPase domains by region 1 of Ras hypervariable regions.Biophysical journal · 2024Article
- Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk.The FEBS journal · 2024Review
- Exploring CRD mobility during RAS/RAF engagement at the membrane.Biophysical journal · 2022Article
- Millisecond molecular dynamics simulations of KRas-dimer formation and interfaces.Biophysical journal · 2022Article
- Phosphatidylserine and Phosphatidylethanolamine Asymmetry Have a Negligible Effect on the Global Structure, Dynamics, and Interactions of the KRAS Lipid Anchor.The journal of physical chemistry. B · 2022Article
- Structural insights into Ras regulation by SIN1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanism of activation and the rewired network: New drug design concepts.Medicinal research reviews · 2022Review
- Intrinsically disordered proteins play diverse roles in cell signaling.Cell communication and signaling : CCS · 2022Review
- Review
- Article
- Membrane-bound KRAS approximates an entropic ensemble of configurations.Biophysical journal · 2021Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Mutant Ras proteins are important drivers of human cancers, yet no approved drugs act directly on this difficult target. Over the last decade, the idea has emerged that oncogenic signaling can be diminished by molecules that drive Ras into orientations in which effector-binding interfaces are occluded by the cell membrane. To support this approach to drug discovery, we characterize the orientational preferences of membrane-bound K-Ras4B in 1.45-ms aggregate time of atomistic molecular dynamics simulations. Individual simulations probe active or inactive states of Ras on membranes with or without anionic lipids. We find that the membrane orientation of Ras is relatively insensitive to its bound guanine nucleotide and activation state but depends strongly on interactions with anionic phosphatidylserine lipids. These lipids slow Ras' translational and orientational diffusion and promote a discrete population in which small changes in orientation control Ras' competence to bind multiple regulator and effector proteins. Our results suggest that compound-directed conversion of constitutively active mutant Ras into functionally inactive forms may be accessible via subtle perturbations of Ras' orientational preferences at the membrane surface.
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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.