Research Areas
Structural Bioinformatics.
We are developing computational methods to calculate the shapes of proteins
and other biological molecules. Our approach uses cutting edge developments
from computational geometry and computational topology. Studies of
protein shapes have two focuses: 1) the surface regions, including
pockets, binding sites, and their precise cast or mold. The goal is to
predict protein-ligand binding, protein-protein interactions and uncover
novel biochemical functions based on full characterization
of protein whole surfaces of the universe of all known protein structures. 2) the interior
packing of proteins, and its relationship with protein stability and folding,
We are also developing empirical statistical potential useful for protein
fold recognition problem and for protein design.
Cheminformatics and Drug Discovery.
We apply an integrated approach for drug discovery. On the small molecule side,
novel shape and chemistry based descripters have been developed to
provide the metrics for managing
chemical diversity of compound database and combinatorial
libraries. On the receptor side, pocket
surface analysis and precise cast of binding site provide additional
rich information
for rapid virtual screening of compounds
to achieve enhanced
enrichment of useful lead compounds. Our approach emphasizes the
physicochemical properties of the molecules rather than bond connectivities,
and we are developing methodology
that allows lead hopping where compounds of related biological activity
but different underlying medicinal chemistry can be identified.
Data Mining.
We are applying various statistical pattern recoginition techniques and
mathematical and statistical methods for classification and prediction
problems arising from high
dimensional data in drug discovery. These include discriminant analysis,
parametric and nonparametric methods, hybrid models, neural nets and analysis tools
complementing PCA and other Gaussian-distribution based methods.
Computational Biology.
We study the molecular electrostatics and solvation problem using
continuum model. We are developing a boundary element method for
the Poisson-Boltzman equation, with emphasis on accurate shape representation,
as well as the application of fast multilevel
method. Of particular interest is the differential treatment of surface
and core region of proteins embedded in solution. In addition, we are
studying osmotic stress related hydration changes during enzyme reaction
to elucidate the relationship of water transfer and enzyme mechanism.