We
seek to understand molecular mechanisms of certain key biological processes,
as well as signal transduction between processes at the level of protein
structure, dynamics, and mechanism. Molecular cloning, expression,
site-directed mutagenesis, and strong focus onto biochemistry are a
key part of the arsenal for defining molecular mechanisms. We focus on
the questions of how signals cross membranes, and how membrane proteins,
and membrane channels work at the level of atomic structure. We also focus
on how the signal recognition particle (SRP) directs membrane and secreted
proteins to the membrane.
Molecular structures are defined primarily by x-ray crystallography.
Design
of drug molecules of specified properties is the quintessential
test of our understanding of the relationship between molecular structure
and affinity. Here methods are being developed to quantitate the relationship
between affinity, and structure concerning molecular interactions.
Several strategically important clinical targets are
foci. These currently include HIV integrase, and second
generation drug design to combat resistance in HIV
protease. Species specific inhibitors of thymidylate
synthase are designed as anti-pathogenic drugs. Neuroreceptors
and hormone receptor systems are being defined at the
cellular and molecular structure levels to understand
the fundamental mechanisms for cell to cell signaling.
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