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                       BIOINFORMATICS COLLOQUIUM
                    School of Computational Sciences
                        George Mason University
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                        Protein-Protein Docking

                         Jeffrey J. Gray, Ph.D.
                  Chemical & Biomolecular Engineering 
                Johns Hopkins University, Baltimore, MD

                       Tuesday, October 5, 2004
                                4:30 pm
               Verizon Auditorium, Prince William Campus

The protein docking problem, that is, the task of assembling two
separate protein components into their biologically relevant complex
structure, is important for several reasons.  First, it is of extreme
relevance to cellular biology, where function is accomplished by
proteins interacting with themselves and with other molecular
components.  Second, the protein docking problem presents a fundamental
test of our understanding of the energetics of macromolecular
interactions, as the native complex structure is almost certainly at a
global free energy minimum.  Finally, an important post-genomic goal is
the characterization of the structures of protein-protein complexes, and
computational tools offer an inexpensive means to carry out large-scale
studies.  I will discuss our latest methods to predict protein-protein
complexes from the coordinates of the unbound monomer components.  The
method (RosettaDock) employs a low-resolution rigid-body Monte Carlo
search followed by simultaneous optimization of backbone displacement
and side-chain conformations using Monte Carlo minimization.  Up to 10^5
independent simulations are carried out, and the resulting "decoys" are
ranked using an energy function dominated by van der Waals interactions,
an implicit solvation model, and an orientation-dependent hydrogen
bonding potential. Top-ranking decoys are clustered hierarchically to
select the final predictions.  The algorithm was tested in an
international blind challenge, the Critical Assessment of PRedicted
Interactions (CAPRI).  Recent notable predictions by our algorithm
include one of the two best structures of the laminin-nidogen complex
(T08) and a correct structure for the complex of cohesin and dockerin
produced using a homology model for the starting structure of dockerin
(T11).  The docking source code and decoy sets (for the development of
scoring functions) are available at graylab.jhu.edu.  Finally, I will
discuss recent explorations into flexible-backbone docking, applications
in therapeutic antibodies, and creative approaches to modeling protein
interactions with solid surfaces.

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Refreshments are served at 4:00 pm.  Find the schedule and directions at
http://www.binf.gmu.edu/colloq.html