The Sanbonmatsu team uses computational and experimental approaches to understand the mechanism of a diverse array of non-coding RNA systems, including ribosomes, riboswitches and long non-coding RNAs. Originally focusing on large-scale simulations of the ribosome, we have expanded into joint computational/experimental studies of riboswitches and purely experimental studies of long non-coding RNAs. The ribosome is one of the few large RNA systems that has been studied mechanistically. We are applying our knowledge gained from ribosome studies to long non-coding RNA systems.
We are performing large-scale molecular simulations of the ribosome to uncover the energy landscape of tRNA selection and translocation. We are using explicit solvent, reduced-model and enhanced sampling methods.
LncRNAs (typically 1-10 kB) play key roles in development and disease and are often involved in epigenetic mechanism. We are using experimental biochemistry appoaches to probe the structure of long non-coding RNAs (lncRNAs).
Riboswitches use competing secondary structures to control gene expression. We are using an integrated experiment/computation approach to understand the role of ligand binding, magnesium and the expression platform in controlling riboswitch conformation.
Structural architecture of the human long non-coding RNA, steroid receptor RNA activator. Novikova IV, Hennelly SP, Sanbonmatsu KY, Nucleic acids research (2012). 40: 5034-51
Magnesium fluctuations modulate RNA dynamics in the SAM-I riboswitch. Hayes RL, Noel JK, Mohanty U, Whitford PC, Hennelly SP, Onuchic JN, Sanbonmatsu KY, Journal of the American Chemical Society (2012). 134: 12043-53
Computational studies of molecular machines: the ribosome. Sanbonmatsu KY, Current opinion in structural biology (2012). 22: 168-74
The expression platform and the aptamer: cooperativity between Mg2+ and ligand in the SAM-I riboswitch Hennelly SP, Novikova IV, Sanbonmatsu KY, Nucleic Acids Research, In press