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