My research utilizes structure-based models for proteins and RNA to understand folding and functional dynamics. A large component of my work has been to extend structure-based models to an all-atom representation. The models we have developed for proteins, RNA, DNA, and some ligands, are freely available through our web-interface.

Recent All-Atom activities:
In our initial investigation using the all-atom structure-based models for proteins we characterized the robustness of the results obtained with this model and the detailed role of side chain packing during protein folding. In summary, we found that backbone folding mechanisms were similar to those obtained using its C-alpha analogue and the folding mechanisms were not largely dependent on folding parameter choices. Though, since this model has atomic resolution, it may be used to understand how atomic interactions give rise to a wide variety of phenomena in protein dynamics. The manuscript can be viewed here.

Using the findings from our studies on proteins, we moved forward and applied our structure-based framework to study RNA folding. The system of interest was the SAM-1 Riboswitch. Since riboswitches adopt specific 3-dimensional conformations upon ligand binding, we had to extend the model so that we could simulate freely associating ligands. To accomplish this, we simulated the system in a bath of "structure-based" ligands (i.e. the ligands are only attracted to the binding site.). With this approach, we identified a non-local helix (i.e. high contact order helix) as the rate limiting step in folding. Further, this study suggested that ligand binding stabilizes this helix and also reduces the free-energy barrier associated with its formation. The manuscript can be viewed here.

CV

An all-atom structure-based potential for proteins: Bridging minimal models with all-atom empirical forcefields, Whitford, P. C., Noel, J. K., Gosavi, S., Schug, A., Sanbonmatsu, K. Y., Onuchic, J. N., Proteins-Structure Function and Bioinformatics, Vol: 75, Iss: 2, pp. 430-441 (2009)

Nonlocal Helix Formation Is Key to Understanding S-Adenosylmethionine-1 Riboswitch Function, Whitford, P. C., Schug, A., Saunders, J., Hennelly, S. P., Onuchic, J. N., Sanbonmatsut, K. Y., Biophysical Journal, Vol: 96, Iss: 2, pp. L7-L9 (2009)