Research
Proteins, nucleic acids, and other long molecular chains fold into unique and complex three-dimensional shapes. Our long-term goal is to be able to predict how these molecules' sequences code for their structures.
The Questions
With its simple four-letter alphabet, its amenability to rapid and cheap synthesis, and its biological importance, RNA is currently the main model molecule in the lab.
- Can the folds of at least the smallest RNA modules be predicted from first principles?
- Can RNA structures be solved at high resolution without crystals or NMR?
- How do real riboswitches integrate multiple cellular signals?
- Do totally random RNA chains have unique tertiary structures?
- Are Watson-Crick base pairs really necessary for RNA structure?
- Can we rationally design nucleic acids that form crystals ordered at atomic resolution?
And going beyond RNA:
- A general solution to the problem of protein structure prediction is tantalizingly close - what's missing?
- What are the 3D structures formed by segments of chromatin, our histone-decorated DNA?
The Approaches
- Nearly any biophysical tool applicable to nucleic acids, from chemical structure mapping to solution x-ray scattering to high-throughput mutagenesis.
- Structure mapping with "bombs" (the MOHCA technology, Multiplexed •OH Cleavage Analysis).
- A new generation of computer algorithms for modeling biomolecules at high resolution - using thousands (and, soon, millions) of CPUs.