Research Interest

Our broad interest is in characterizing the structural dynamics of functional biomolecules by deploying a state-of-the-art, integrative modeling approach to study their biophysical properties. Below is a list of more specific research interest.

MicroRNAs Biogenesis and Gene Silencing

MicroRNAs are a new class of RNAs that are associated with many devastating human diseases. Current efforts are geared towards developing an integrative modeling and simulation approach — which will make use of primary experimental output from NMR spectroscopy, single-molecule FRET, Mass spectroscopy, chemical cross-linking, chemical footprinting, and circular dichroism, for example — to study the spatiotemporal properties of microRNAs. Using a multi-scale modeling approach, we will also focus on understanding the role that structure and dynamics play in coordinating messenger RNA repression by studying microRNAs in the context of the RNA-induded silencing complex (RISC). Our group will play particular attention to microRNAs implicated in various forms muscular dystrophy (e.g., Duchenne muscular dystrophy), cancer (e.g., Prostrate Cancer), neurological diseases (e.g., Parkinson’s diseases), and infectious diseases (e.g., HIV).

Improving “Pure” Modeling and Simulations of RNAs

The human genome contains more than 10,000 small functional RNAs. To understand the function of these RNAs, we need to understand their 3-dimensional structure and dynamics. As such, there is a need to develop computational methods that enable the structure and dynamics of RNAs to be rapidly characterized. Current efforts in our group center on using predictive modeling tools to developed better quality prediction methods to improve the reliability of RNA structure prediction, and secondly, developing better classical force fields (in particular, NMR-optimized force fields) for atomistic simulations of RNA. Improvements on these fronts, coupled with advancements in computer software and hardware, will enable the structure and dynamics of newly discovered RNAs to be rapidly characterized.

Other Areas of Interest

Deciphering the mechanism of action of RNA-protein machines by studying their structural dynamics; unraveling the dynamical aspects of small-molecule recognition by RNA targets; understanding drug binding by studying their solution dynamics; developing novel RNA-ligand scoring methods for use in structure-based drug discovery; understanding the structural and functional consequences of base modifications in nucleic acids, particularly in the context of RNA interference; and using a simulation-driven approach to design more effective and drug-resistant RNA targeting antibiotics.