The RNA letter code expands way beyond the canonical four nucleobases - A, C, G, U. Of the ~150 naturally occurring RNA modifications that have been discovered, several of them are found in tRNAs. The modifications range from replacing a carbonyl oxygen atom with a sulfur to the addition of elaborate groups (like a 12 carbon long geranyl group),  The translation machinery relies on modifications and wobble decoding to improve translation fidelity and efficiency. We use molecular dynamics simulations to study the structural effects of RNA modifications with functional implications pertaining to prokaryotic/ eukaryotic and viral systems in translation and reverse transcriotion respectively. 

Structure based virtual screening is an integral part of any in silico drug design and discovery pipeline. Further molecular modeling and simulations can also be useful in proposing modifications to improve binding, solubility and other desirable drug properties. We use a combination of molecular docking and molecular dynamics simulations including enhance sampling methods to understand drug binding to RNA with a focus on myotonic dystrophy therapeutics. 

Drug delivery systems are an integral and important part of any drug development pipeline. As drugs have evolved from small molecules to now include proteins, peptides and more recently nucleic acids, the drug delivery systems have also diversified to fit the needs. While small molecules enjoy the advantage of easy diffusibility through most biological fluids and membranes, often low solubility, leading to high dosage or low bioavailability is a concern. Several types of materials have been explored as drugdelivery systems but have drawbacks including lack of targeting capabilities, inhomogeneous size etc. DNA nanostructures are biocompatible, induce minimal immunological response, can enter cells without the need for transfection agents, and be targeted to specific cells, allowing controllable and localized drug release. We use a combination of sequential docking and molecular dynamics to develop a pipeline for testing and optimizing different nanostructure:small molecule combinations for drug delivery.