Date of Award




Document Type


Degree Name

Doctor of Philosophy (PhD)


Department of Biomedical Sciences

Content Description

1 online resource (vii, 234 pages) : color illustrations

Dissertation/Thesis Chair

Nilesh K Banavali

Committee Members

Randall Morse, Janice Pata, Angel Garcia, Joachim Jaeger


base stacking, clustering, molecular dynamics, nucleic acids, rate calulations, structural analysis, Nucleic acids, RNA, Molecular dynamics

Subject Categories

Biochemistry | Bioinformatics | Biophysics


Base stacking provides stability to nucleic acid duplexes, and base unstacking is involved in numerous biological functions related to nucleic acids, including replication, repair, transcription, and translation. The patterns of base stacking and unstacking in available nucleic acid crystal structures were classified after separation into their individual single strand dinucleotide components and clustering using a k-means-based ensemble clustering method. The A- and B-form proximity of these dinucleotide structures were assessed to discover that RNA dinucleotides can approach B-form-like structures. Umbrella sampling molecular dynamics simulations were used to obtain the potential of mean force profiles for base unstacking at 5'-termini for all 16 dinucleotides. A rate calculation method was investigated and implemented using small test compounds and applied to a base unstacking transition to predict a rate for 5'-terminal base fraying. The findings can be applied for localized nucleic acid structure prediction, and for comparison of molecular dynamics simulation-based investigations of nucleic acid distortions to experimental structural data.