Like many other Hopkins biophysicists, I work on protein
structural biology problems. Proteins and some RNA molecules are life's
chemical engines. In order to perform their specific and complex biological
functions, proteins must achieve a well-ordered three-dimensional structure.
However, a protein is synthesized in an unfolded form based on the gene that
encodes it, and the three-dimensional form of the protein forms spontaneously
out of this unfolded form. Many computational biophysicists like myself
are interested in "structure prediction," that is, predicting this folded
structure of the protein based on its sequence without having to determine
its structure experimentally. Much information can be derived from
a protein's three-dimensional structure, but there is much more to a cell,
even more to an organism, than the structures of all of its proteins.
Many proteins must alter their function, and hence their structures, in response
to some environmental change; this is the problem of regulation. In
addition, proper function of cells and organisms requires cells from different
parts of the organism to act synchronously, and proteins within cells to
communicate with each other through a process known as signal transduction.
These signaling pathways are involved in such processes as cell division
regulation, optical and olfactory response, and hormone response. Improper
functioning of these pathways can lead to disease; for example, the malfunction
of cell cycle control is the primary cause of many cancers. Signal
transduction is just regulation on a higher level, not involving just the
response of a single protein to environmental conditions, but often a whole
network of proteins. On the biomolecular level, I refer to this as
the problem of "structural sensitivity." For example, how does a drug
alter the structure of a biochemically important protein in order to inhibit
that protein and treat a disease? My work focuses on the extension of an
existing structure prediction algorithm known as Rosetta to simulate how
protein structures respond to binding a small molecule or another protein.