Measurements of Conformational Penalties in Nucleic Acids
Date
2021
Authors
Advisors
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Abstract
Biomolecules are dynamic entities that adopt a variety of conformations in solution. Conformational changes in biomolecules routinely take place when they take part in biochemical processes such as binding and catalysis. The energetic cost or conformational penalty to adopt an alternative conformation, which typically is paid for by thermal fluctuations or inter-molecular contacts with a partner molecule, can be an important determinant of these efficacy and selectivity of these biochemical processes. These conformational penalties can also be modulated by changes in physiological conditions and chemical modifications, enabling fine control over these biochemical processes, and aberrant changes to these conformational penalties can also be associated with disease. Thus, measurement of conformational penalties in biomolecules and how they can be tuned by external cues are essential to understand the role of conformational dynamics in biology.In this thesis, a combination of experimental and computational techniques such as NMR spectroscopy, UV melting and MD simulations are used to measure conformational penalties in nucleic acids and how they are modulated by post-transcriptional and epigenetic modifications, with particular applications to the formation of Watson-Crick like mismatches in DNA, and Hoogsteen base pairs in RNA and DNA. Improved methods that enable measurements of these conformational penalties with increased throughput and sensitivity, involving the use of NMR spectroscopy and UV melting, are also presented.
Type
Department
Description
Provenance
Citation
Permalink
Citation
Rangadurai, Atul Kaushik (2021). Measurements of Conformational Penalties in Nucleic Acids. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/23729.
Collections
Except where otherwise noted, student scholarship that was shared on DukeSpace after 2009 is made available to the public under a Creative Commons Attribution / Non-commercial / No derivatives (CC-BY-NC-ND) license. All rights in student work shared on DukeSpace before 2009 remain with the author and/or their designee, whose permission may be required for reuse.