Abstract
The discovery of several non(protein)coding RNAs, which directly participate in structural, catalytic or regulatory functions, have drawn progressively greater scientific attention to RNA studies. Since molecular structures strongly correlate with functions of
biomolecules, a lot of interest has been generated towards detailed molecular level understanding of RNA structures. With the advancement in crystallographic and NMR techniques, high resolution structure of several noncoding RNA molecules have been reported since last decade. These include ribozymes, t-RNAs, group I and group II introns, riboswitches and even the ribosome itself. In this context, with the advent of new biophysical techniques
on the one hand and enhancement in computational power on the other, progressively larger amounts of data addressing the structure-function paradigm of RNA molecules are being
generated on a regular basis. In silico analysis of these data, has the potential to address many of the important biological problems. For automated and high throughput analysis of available
experimental data, it is important to facilitate their retrieval as per the requirements and implementation of efficient algorithms to analyze this data from various perspectives. All this
has led to the rapid emergence of the new research domain of “RNA Structural Bioinformatics”, which in the larger context, bridges the gap between the RNA structural biology and the bioinformatics communities. In other words, it can be said that the domain
Structural Bioinformatics bring the complementary, and yet largely separated, areas of computational investigations involving structure, dynamics, and functions within a single
comprehensive fold. The work described in this thesis addresses different important aspects of RNA structural bioinformatics research, involving detailed structural and contextual analysis of RNA structural elements, which can facilitate the formulation of rules governing the remarkable structural and functional diversities of large RNA molecules. To understand the complex RNA
structures and respective functions, a bottom-up approach is followed in my work, where characterization of the smaller and simpler structural elements have been carried out first to
understand their putative functional roles in overall structural contexts. With the larger goal of strengthening the basis for future research within the RNA structure-function paradigm, the
scope of this thesis may be defined, though not limited, by the following specific objectives: (i) meaningful annotation and classification of higher order RNA structural elements
(assemblies of more than one nucleotide residues connected by base-pairing interactions), (ii) implementation of different algorithms for mining recurrent structural elements present in larger RNA molecules, (iii) systematic organization of available data related to occurrences, structures and stability of different RNA structural elements and development of databases which can interactively support complex queries for easy retrieval of customized information, and (iv) computational study to understand the stability of few important RNA structural elements using quantum mechanical (QM) methods. In addition, to demonstrate the importance of the work done for this thesis, a thorough background study has been carried out and reported. This provides a comprehensive review, highlighting the landmarks in the course of
developments leading to its contemporary status, in the field of RNA structural bioinformatics.