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Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Novel Statistical Analysis and Modeling of Mechanical Unfolding of Proteins

Mechanically active proteins are usually organized as homogeneous (D-D-...-D) or heterogeneous (D1-D2-...-Dn) tandems of domains (D?s). In pioneering atomic force microscopy experiments mechanical unfolding of protein tandems is studied by using constant stretching force (force-clamp mode). The observable quantities are first, second, third, et cetera, unfolding times that mark unfolding transitions of individual domains. The main goals of these experiments are (i) to obtain the distributions of unfolding times for individual domains and (ii) to map the unfolding energy landscape. Currently, simplistic statistical analyses are used that limits the scope of the potential information gains. Tailoring of existing and the development of new statistical tools for the analysis and modeling of unfolding data are much needed. We present a new methodology for the analysis of unfolding transitions, which is based on statistical analysis of ordered variates (unfolding times), and order statistics probability densities of unfolding times. The formalism allows (I) to probe interdomain interactions, which results in recently observed domain stabilization and cooperativity, and (II) to map out the multidimensional unfolding energy landscape of interacting proteins.

Valeri Barsegov

Department of Chemistry
University of Massachusetts Lowell
Lowell, MA 01854

Phone: 978-934-3661
Fax: 978-934-3013
Email: Valeri_Barsegov@uml.edu