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The larger question is to understand the rules governing the structure and dynamics of functional RNA. The following two hypotheses define the basis for our research in this area:
- Noncanonical base pairs play significant roles in shaping the structure and function of RNA
- Understanding the interaction energies and the stabilities of noncanonical base pairs can help in their classification in terms of their roles
The strategy involves
Database Analysis
- Extraction and classification of noncanonical base pairs from non redundant set of RNA crystal structures according to geometric families
- Evaluation of occurrence frequency and analysis of their context
- Classification of contexts in terms of higher order structural modules and participation in functions
Quantum chemical computation:
- Extraction of crystal geometries of representatives from each base pair family
- Evaluation of changes in geometries and interaction energies on relaxed optimization
- Correlation of results with occurrence context and nature of hydrogen bonding
- Evaluation of interaction energies in higher order structures
Molecular dynamics simulation:
- Crystal geometries of modular 3D motifs and aptamer domains as initial structures for molecular dynamics simulations
- Analysis of simulation trajectories for ‘apo’ and ‘holo’ structures under different simulated experimental conditions
Specific activities in this area include:
- 3D motif mining in functional RNA structures
- Tools to visualize RNA torsion and interaction data
- Application of Graph theory approaches to represent and analyse RNA molecular dynamics simulation data.
- Ab initio quantum chemical computations to elucidate the geometries and interaction energies of noncanonical base pairs in RNA
- In silico methods targeted towards understanding the structure, stability, dynamics of RNA riboswitches and to design engineered riboswitches
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