Research overview

We are interested in exploring molecular mechanisms in biology and chemistry. In particular, we are interested in uncovering physical principles that govern the conformational transitions in proteins and nucleic acids. How do proteins and RNA’s fold? How do environmental factors influence the folding pathways? What are the origins, features, and effects of the denatured-state interactions? How can we harness the physical principles for controlling disease states as well as for protein design and engineering?

In recent years, misfolded proteins and structured aggregates have been implicated in a class of disorders, such as Alzheimer’s, Parkinson’s and mad cow diseases, underscoring the need for molecular-level understanding of protein folding. While advances in protein engineering and other experimental techniques have been leading the way in mapping folding pathways of proteins, significant progress has also been made in theoretical investigations. Notably, the folding funnel theory has offered a theoretical foundation for the prediction of protein folding pathways using molecular simulations with native-structure based potential energy functions. Folding simulations of small proteins at atomic resolution has been realized with physics-based force fields and implicit solvent models.

Guided by classical, statistical and quantum mechanical theories, we are developing theoretical methods and implementing them in computer simulations to elucidate molecular mechanisms in various biological and chemical phenomena. Current topics include denatured-state effects on protein stability and folding; microscopic electrostatics in proteins; titration properties of surfactant micelles; the role of pH and metal-ion binding in protein folding and amyloid formation; conformational dynamics of RNA; and improved force fields for folding of proteins and nucleic acids.

News & Highlights

Nov 2009

Feb 2009 - Students from the CCB class participate in the first worldwide blind prediction of protein pKa's

Sept 2008 - Research from University of Oklahoma in enzyme research provides new insights

Feb 2008 - "Exceptional" paper, evaluation on "Faculty of 1000 Biology"

Oct 2007 - Papers of the week: A new alternative "endosomic" amyloid hypothesis

Oct 2007 - News and Views from the Scripps Research Institute: The Goldilocks Scenario