Date of Award

Winter 12-2019

Document Type

Honors Thesis

Degree Name

Bachelor of Science

Department

Chemistry

Advisor/Committee Chair

Alan A. Chen, Ph.D.

Committee Member

Parisa Ebrahimi

Committee Member

Chris Meyers, M.A.

Abstract

Many recent theoretical and experimental techniques have been developed to probe the structurefunction relationships of complex biomolecules. The roles of RNAs are dependent upon various intricate structural motifs and interactions, including hairpins, pseudoknots, long range territory contacts, bulges and internal loops, that are not easily captured by these methods. We had previously developed an enhanced replica exchange molecular dynamics method that incorporated secondary structure information in the form of distance restraints in order to effectively overcome kinetic barriers and sample conformational space. In several structures, restrained RNA base pairs near large bulges displayed a preference for stacking over hydrogen bonding in simulation. This persisted after usage of numerous enhanced sampling methods. Since RNA tertiary structure is scaffolded by a complex hydrogen bonding network, an accurate depiction of directional hydrogen bonding is essential to obtain predictive nucleic acid models. We compared gas phase DFT and molecular mechanics energies for cytosine-guanine nucleobases and nucleosides in order to determine the accuracy of the classical depiction of hydrogen bonding and evaluate the need for an explicit hydrogen bonding potential for nucleic acids.

Included in

Chemistry Commons

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