{"677676":{"#nid":"677676","#data":{"type":"event","title":"Colloquium Seminar - Prof. Qiang Cui (Boston University)","body":[{"value":"\u003Cp\u003E\u003Cem\u003E\u003Cstrong\u003EAnalysis of Allostery in a Transcription Factor Using Molecular Simulations and Machine Learning\u0026nbsp;\u003C\/strong\u003E\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003E\u0026nbsp;Abstract:\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; \u0026nbsp;\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EWhile allostery has been a topic of intense interest for the past several decades, our understanding of the underlying mechanism at the molecular level continues to be challenged by new experimental observations. Specifically, a recent deep mutational scanning study of a bacterial transcription factor TetR found that allostery hotspot residues are broadly distributed over a major portion of the protein structure, rather than being clustered near the ligand-binding and DNA-binding domain interfaces as often discussed in structure-based studies. Similarly, loss of inducibility due to mutation of hotspots could be rescued by additional mutations that were also broadly distributed throughout the protein. These findings suggest that the contributions of hotspot residues are unlikely explained by a single mechanism, thus calling for different analysis strategies compared to previous computational studies.\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EIn this seminar, I\u2019ll discuss our recent efforts that integrated atomistic simulations, machine learning analysis and a thermodynamic (MWC like) model to explain the various aspects of the experimental findings. The key realization from these analyses is that allostery hotspots may contribute by either mediating inter-domain communications or intra-domain energetics. The mechanistic insights we gleaned for TetR might be broadly applicable to allosteric systems with the similar structural topology.\u0026nbsp;\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003Cstrong\u003ERelevant references:\u0026nbsp;\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EA parametrized two-domain thermodynamic model explains diverse mutational effects on protein allostery, Z. Liu, T. Gillis, S. Raman, Q. Cui*, \u003Cem\u003EeLife\u003C\/em\u003E, 12, RP92262 (2024) \u0026nbsp;\u003C\/p\u003E\u003Cp\u003EModulation of Allostery with Multiple Mechanisms by Hotspot Mutations in TetR, J. Deng*, Y. Yuan and Q. Cui*, \u003Cem\u003EJ. Am. Chem. Soc.\u003C\/em\u003E 146, 2757-2768 (2024) \u0026nbsp;\u003C\/p\u003E\u003Cp\u003EDeep mutational scanning and machine learning reveal structural and molecular rules governing allosteric hotspots in homologous proteins, M. Leander\u2021, Z. Liu\u2021, Q. Cui* and S. Raman*, \u003Cem\u003EeLife\u003C\/em\u003E, 11, e79932 (2022) \u0026nbsp;\u003C\/p\u003E\u003Cp\u003EMolecular Dynamics Simulations Establish the Molecular Basis for the Broad Allostery Hotspots Distribution in the Tetracycline Repressor,\u0026nbsp; Y. Yuan\u2021, J. Deng\u2021 and Q. Cui*, \u003Cem\u003EJ. Am. Chem. Soc\u003C\/em\u003E., 144, 10870-10887 (2022)\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EFunctional Plasticity and Evolutionary Adaptation of Allosteric Regulation, M. Leander, Y. C. Yuan, A. Meger, Q. Cui and S. Raman*, \u003Cem\u003EProc. Natl. Acad. Sci. USA\u003C\/em\u003E, 117, 25445-25454 (2020)\u0026nbsp;\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EOne in the series of the SoCB seminars.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"School of Chemistry \u0026 Biochemistry -Seminar Series"}],"uid":"36441","created_gmt":"2024-10-16 18:46:20","changed_gmt":"2024-10-21 12:29:52","author":"slawrence67","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2024-11-07T15:30:00-05:00","event_time_end":"2024-11-07T16:30:00-05:00","event_time_end_last":"2024-11-07T16:30:00-05:00","gmt_time_start":"2024-11-07 20:30:00","gmt_time_end":"2024-11-07 21:30:00","gmt_time_end_last":"2024-11-07 21:30:00","rrule":null,"timezone":"America\/New_York"},"location":"MoSE - G011","extras":[],"groups":[{"id":"85951","name":"School of Chemistry and Biochemistry"}],"categories":[],"keywords":[],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1795","name":"Seminar\/Lecture\/Colloquium"}],"invited_audience":[{"id":"78761","name":"Faculty\/Staff"},{"id":"177814","name":"Postdoc"},{"id":"174045","name":"Graduate students"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Cstrong\u003EHost\u003C\/strong\u003E: Prof. Lynn Kamerlin\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}