chapter_03.md

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default		true	islands.jpg	Chapter 3	Unknown Knowns, Known Unknowns, and Unforeseen Consequences: Using Free Energy Shifts To Predict Mutant Phenotypes	title title_url external_url description Summary false Here, I present a biophysical model of allosteric transcriptional regulation that directly links the location of a mutation within a repressor to the biophysical parameters that describe its behavior. Here, we explore the phenotypic space of a repressor with mutations in either the inducer binding or DNA binding domains. Using the LacI repressor in <i>Escherichia</i> <i>coli</i>, we make sharp, falsifiable predictions and use this framework to generate a null hypothesis for how double mutants behave, given knowledge of the single mutants. Linking mutations to the parameters which govern the system allows for quantitative predictions of how the free energy of the system changes as a result, permitting coarse graining of high-dimensional data into a single-parameter description of the mutational consequences.	prev next content url Chapter II chapter_02 content url Chapter IV chapter_04	chapter_03	section_01_header section_02_abstract section_03_introduction section_04_model section_05_DNA_mutants section_06_IND_mutants section_07_DBL_mutants section_08_discussion section_09_methods

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