ArticlePLoS computational biology2026
Computational insights on the molecular interplay between KRas (G12D mutation) and SOS1 modulated by the inhibitor BI-3406.
Article in PLoS computational biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
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.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ras proteins are prominent oncogenes, with KRas mutations found in approximately 80% of cancer cells harboring Ras mutations. The mechanism by which Ras mutations cause cancer remains unclear. Human Son of Sevenless (SOS) promotes the GDP-to-GTP exchange in the inactive GDP-bound Ras (RasGDP) by interacting with RasGDP conformation, thereby leading to the development of human cancer. Elucidating the Ras-SOS interaction mechanism can guide the drug design for Ras and SOS proteins. Based on our previously sampled special structure KRasGDP·Mg2+S1.2, this study constructs a functional ternary complex (KRasGDP·Mg2+)·SOS1·(KRasGTP·Mg2+). Furthermore, the KRas-SOS1 interactions regulated by the KRas G12D mutation and the SOS1 inhibitor BI-3406 that reportedly exhibits synergistic effects with G12D-mutant Ras inhibitors, are investigated through molecular dynamics (MD) simulations. The findings reveal that the G12D mutation and BI-3406 both affect the KRas-SOS1 interaction via the Switch-II (SW2) region of KRas. The negatively charged Asp12 has a repulsive effect on KRas, particularly on SW2, altering the interfacial electrostatic landscapes and diminishing the binding affinities by approximately 25 kcal/mol for both KRasGDP·Mg2+ and KRasGTP·Mg2+. BI-3406 forms a hydrogen-bond bridge between SW2 and SOS1 in wild type (WT) KRas, interrupting the interactions among the N-terminal residues of SW2 and SOS1. Moreover, BI-3406 was found here to attenuate the binding affinity of both WT and G12D-mutant KRasGDP·Mg2+ to SOS1. Interestingly, BI-3406 hardly affects the binding affinity of WT KRasGTP·Mg2+, while enhances the binding affinity of G12D-mutant KRasGTP·Mg2+. The change of binding affinity makes the catalytic pocket of SOS1 prefer to KRasGTP·Mg2+ and inhibits the growth of G12D-mutant KRas-driven tumors. These mechanistic insights provide valuable information for designing SOS1-co-targeting inhibitors to potentiate antitumor efficacy against G12D-mutated KRas.
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.