2026-10-13T12:24:08Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33803955 2026-09-15T15:46:49Z category_1 category_4 category_915 category_7 category_14 category_15 category_19 category_24 category_873 category_734 category_64 portal_63 item_type_2 month_year_09_2026

Semi-Automated Discovery of Structural Elements Controlling GPCR Function Jingjing Ji (1597363) Edward Lyman (1858066) Biophysics Biochemistry Physical Sciences not elsewhere classified Medicine Molecular Biology Neuroscience Pharmacology Evolutionary Biology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Cancer structural biology toolkit previously reported motion performs unsupervised clustering opening new opportunities like ” motion featurized simulation data experimental structures alone accompany functional transitions coupled “ piston known structural elements identifies several well automated analysis pipeline coupled receptors automated discovery revealing structure reproducible observations obtain trajectories large set known microswitches input features important part function mechanisms cluster identity Molecular simulations of G-protein-coupled receptors have become an important part of the structural biology toolkit, revealing structure-function mechanisms that are unobservable from experimental structures alone. With the advance of hardware and software, it has become routine to obtain trajectories that are tens of microseconds in duration, opening new opportunities for yet more rigorous and reproducible observations on mechanism. Toward this end, we presented a semi-automated analysis pipeline which operates on featurized simulation data, performs unsupervised clustering, and then identifies which input features are most discriminatory of cluster identity. Application of this pipeline to a large set of G-protein-coupled receptor simulation data shows that it identifies several well-known microswitches. Inspection of these structural elements reveals changes in conformation that are known to accompany functional transitions of the receptor. In addition to these known structural elements, the analysis also identifies functional transitions associated with one new motifthe kink in transmembrane helix 2and discovers a coupled “piston-like” motion of TM2 and TM3 that elaborates a previously reported motion of TM3. 2026-09-15T00:00:00Z Dataset Media 10.1021/acs.jcim.6c01584.s002 https://figshare.com/articles/media/Semi-Automated_Discovery_of_Structural_Elements_Controlling_GPCR_Function/33803955 CC BY-NC 4.0