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                    BIOINFORMATICS COLLOQUIUM
                       College of Science
                     George Mason University
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  Analyzing forced unfolding of protein tandems by ordered variates:
                       Theory and applications
 

                          Dr. Valeri Barsegov

                  University of Massachusetts Lowell


ABSTRACT 
Statistical analyses of forced unfolding data for protein tandems, i.e. unfolding
forces (force-ramp) and unfolding times (force-clamp) presently used in single-molecule
dynamic force spectroscopy, rely on the ``iid-assumption'' that the unfolding
transitions of individual protein domains are independent (uncorrelated) and characterized,
respectively, by identically distributed unfolding forces and unfolding times. We show that
in the experimentally accessible pico-Newton force range, the iid-assumption may break.
We develop much needed statistical tests for assessing the independence of the
unobserved forced unfolding times for individual protein domains in the tandem and
equality of their parent distributions, which are based solely on the observed ordered
unfolding times. The use and performance of these tests are illustrated through the
analysis of unfolding times for computer models of protein tandems. The proposed tests
can be used in force-clamp AFM experiments to obtain accurate information on protein
forced unfolding, and to probe data on the presence of interdomain interactions.