We are developing improved methods for simulating the folding of RNA motifs at atomistic detail. In recent work, we are able to fold small RNAs including non-canonical interactions to Angstrom-level resolution from the unfolded state. The ability to use physics-based simulations to predict complex, 3D structures of RNA from first principles will have numerous applications in structural biology and biophysics where traditional experimental determinations methods are not adequate. We are currently using these models to study the structures of the untranslated regions of viral genomes such as HCV and Zika Virus inb collaboration with the virology lab of Dr. Cara Pager

  Molecular simulations are only as accurate as their underlying potential energy functions. Quantum chemical calculations are particularly powerful for revealing where semi-classical atomic models break down and also reveal how they can be corrected. At left, DFT calculations reveal thevextent of charge polarization (colored contours) induced by formation of a GC base-pair. Such effects would not be captured in a fixed-partial charge electrostatic model.

We are developing atomistic models of RNA-graphene interactions in collaboration with Mehmet Yigit’s nanobiosensing lab, which we will use to design highly sensitive and specific probes for detecting trace RNA signatures of human diseases. This technology is also being used to design graphene-based nanopore detectors, in collaboration with the College of Nanoscale Science and Engineering.

We are developing simulation models for interpreting and predicting RNA chemical probing experiments (i.e. SHAPE-seq) in collaboration with synthetic biologists in the Lucks lab at Northwestern University,  department of Chemical Engineering. The rational design of synthetic bacterial gene networks will enable the next generation biosensors and biotechnological tools.

 

 

We are developing models to predict the conformation dependent arrival times for RNA in collaboration with the Fabris mass-spec lab. In recent work, we show that long, highly charged polymers such as RNA require improved algorithms to accurate predict their collision cross section. We are also developing gas-phase, fluctuating charge models to simulate the behavior of RNA under gas phase drift-cell conditions experienced during the mass-spec experiment. This will enable IM-MS to be used as a fast and sensitive method for characterizing RNA conformational changes and high-throughput screening of therapeutic compounds.

 

 

 In collaboration with the Li single-molecule lab and the Fabris mass-spec lab, we are using molecular dynamics simulations to explain the force-dissociation pathway for the dimerization initiation site (DIS) of retroviruses such as HIV. More broadly, we are very interested in how simulations can be used to complement single-molecule biophysical experiments in order to characterize weak tertiary RNA interactions and alternative RNA folds that are difficult to predict using standard bioinformatic methods.  At left is a video showing a proof-of-concept study simulating the force-dissociation of the 2-bp MMLV DIS.