The applications of Chemically Accurate Contact Response Analysis (ChACRA) to the study of protein dynamics and allostery

dc.contributor.advisor Potoyan, Davit
dc.contributor.advisor Venditti, Vincenzo
dc.contributor.advisor Nelson, Scott
dc.contributor.advisor Moss, Walter
dc.contributor.advisor Roche, Julien
dc.contributor.author Burns, Daniel
dc.contributor.department Biochem, Biophysics, and Molecular Biology en_US
dc.date.accessioned 2024-06-05T19:02:48Z
dc.date.available 2024-06-05T19:02:48Z
dc.date.issued 2024-05
dc.date.updated 2024-06-05T19:02:49Z
dc.description.abstract Protein dynamics are central to their function. Enzymes must sample a range of conformations that preferentially bind substrate, order reactive groups for catalysis, and release products. The same fundamental principle applies to proteins which regulate their substrate affinity to maintain cellular conditions and communicate signals. Understanding how a protein’s sequence and structure influence dynamics remains a fundamental challenge in biophysics with major implications for de novo protein design and therapeutic development. This dissertation details a novel computational method that reveals an underlying feature of proteins connecting sequence, structure, and dynamics. After sampling a protein’s conformations at many reduced Hamiltonians (effective temperatures), all of the inter-residue contact probabilities are obtained as a function of energy. Principal component analysis is applied to reveal energy-dependent contact patterns. Correlated and highly energy-sensitive interactions are revealed by large magnitude loading scores on the principal components. This Chemically Accurate Contact Response Analysis (ChACRA) and its application to investigations of enzymatic activity tuning, heat sensing, and allostery in several protein systems is discussed.
dc.format.mimetype PDF
dc.identifier.doi https://doi.org/10.31274/td-20240617-66
dc.identifier.orcid 0000-0003-0739-2070
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/ywAbZRlv
dc.language.iso en
dc.language.rfc3066 en
dc.subject.disciplines Biophysics en_US
dc.subject.keywords Allostery en_US
dc.subject.keywords ChACRA en_US
dc.subject.keywords Protein Design en_US
dc.subject.keywords Protein Dynamics en_US
dc.title The applications of Chemically Accurate Contact Response Analysis (ChACRA) to the study of protein dynamics and allostery
dc.type article en_US
dc.type.genre dissertation en_US
dspace.entity.type Publication
thesis.degree.discipline Biophysics en_US
thesis.degree.grantor Iowa State University en_US
thesis.degree.level dissertation $
thesis.degree.name Doctor of Philosophy en_US
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