Synthetic Transcription Factor Allostery Mapping and Analysis

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Berry, Andre D.
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School of Chemical and Biomolecular Engineering
School established in 1901 as the School of Chemical Engineering; in 2003, renamed School of Chemical and Biomolecular Engineering
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Abstract
This work aims to advance the synthetic design of allosterically regulated systems by extracting sequence-function correlations from engineered LacI-based anti-repressors. Through deep mutational scanning, we have generated comprehensive datasets correlating single-mutant genotypes with functional phenotypes. Building upon the experimental dataset and alongside ongoing machine learning efforts that utilize it, I introduce a novel approach to complement these analyses. By projecting deep mutational scanning data onto a representative protein structure model, I enable visual inspection and procedural analysis of position-based relationships. This projection, combined with quantitative data analysis across multiple datasets, generates a comprehensive, site-specific value list that can be algorithmically manipulated. This integrated approach, blending structural visualization with quantitative analysis, provides a deeper understanding towards position linked factors integral in LacI allostery. Ultimately, this research seeks to establish a foundation for improved engineering strategies for synthetic transcription factors and to enhance the development of associated machine learning models by further elucidating the mechanistic underpinnings of anti-repressor function and contributing to the broader understanding of protein allostery.
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Date
2025-07-22
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