Leslie A. Kuhn
Research Interests (also see Kuhn Lab Pages)
Through computational analysis of molecular structures, our research group
seeks to understand how proteins fold, recognize and bind other molecules.
We use this knowledge for optimizing protein and inhibitor/drug design, and
collaborate with researchers in computer science, physics, mathematics,
chemistry, molecular biology, and medicine. Our focus is on decoding the
factors contributing to intra-protein and protein-ligand interactions,
including flexibility and solvation.
A major project in our lab, funded by an NIH Mathematics in Biology grant,
focuses on modeling the flexibility of proteins and their partners (ligands)
during binding. We have developed software to predict the flexible regions
in proteins based on their network of covalent and non-covalent interactions
(including hydrogen bonds and hydrophobic contacts) and use this flexible
network to sample the full range of shapes, or conformations, that the
proteins and their ligands can adopt. Our SLIDE software then predicts how
these flexible molecules interact and scores how tightly they bind. This
highly efficient approach allows structure-based screening of hundreds of
thousands of potential inhibitors, as candidates for drug development to
block proteins associated with cancer, blood clotting disorders, and
infectious diseases. The ability to accurately model conformational change
of both proteins and their ligands will help us design new inhibitors that
are conformationally specific, as well as model protein-ligand recognition
as it truly occurs: as recognition between conformational ensembles. A key application is inhibitor design for proteins implicated in third-world parasitic diseases such
as elephantiasis and malaria, a project funded by NIH in collaboration with
Michael Kron (Medicine).
Recent Publications
Please click on the Publications menu at http://www.kuhnlab.bmb.msu.edu/