{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["6(2)"],"submitter":["Hu Z"],"pubmed_abstract":["KRAS is among the most frequently mutated oncogenes in human cancers, with codon 12 representing a dominant hotspot. Despite decades of study, the atomic-level conformational dynamics of KRAS and its G12 mutations remain insufficiently resolved, posing a central barrier to rational drug discovery. Elucidating these dynamics is critical for revealing hidden druggable pockets and enabling the development of mutation-specific inhibitors. Here, we delineate the impact of KRAS G12 mutations on conformational dynamics and GTP binding by performing microsecond-scale, well-tempered metadynamics simulations. This approach yielded precise free energy landscapes that expose mutation-specific alterations to structural states. By introducing biologically meaningful collective variables, including key a"],"journal":["JACS Au"],"pagination":["830-846"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12933348"],"repository":["biostudies-literature"],"pubmed_title":["Impact of KRAS-G12 Mutations on the KRAS-GTP Bound Conformational Dynamics: Structure, Free Energy Barriers and Drugging Pockets."],"pmcid":["PMC12933348"],"pubmed_authors":["Sha Z","Hu Z","Guo SJ","Tao SC","Marti J"],"additional_accession":[]},"is_claimable":false,"name":"Impact of KRAS-G12 Mutations on the KRAS-GTP Bound Conformational Dynamics: Structure, Free Energy Barriers and Drugging Pockets.","description":"KRAS is among the most frequently mutated oncogenes in human cancers, with codon 12 representing a dominant hotspot. Despite decades of study, the atomic-level conformational dynamics of KRAS and its G12 mutations remain insufficiently resolved, posing a central barrier to rational drug discovery. Elucidating these dynamics is critical for revealing hidden druggable pockets and enabling the development of mutation-specific inhibitors. Here, we delineate the impact of KRAS G12 mutations on conformational dynamics and GTP binding by performing microsecond-scale, well-tempered metadynamics simulations. This approach yielded precise free energy landscapes that expose mutation-specific alterations to structural states. By introducing biologically meaningful collective variables, including key a","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-16T22:58:19.047Z","creation":"2026-07-12T03:09:34.131Z"},"accession":"S-EPMC12933348","cross_references":{"pubmed":["41755851"],"doi":["10.1021/jacsau.5c01097"]}}