Finding inhibitors of the HIV-1 Dimerization Initiation Site

 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.

Predicting RNA Structure & Folding Pathways

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



Designing RNA-based Nano-biosensors

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.

Deducing functional RNA Dynamics from Chemical Probing

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.