[Colloquium] TTIC Talk: Brian Chen, Columbia University

[Julia MacGlashan]

When:             *Thursday, Apr 1 @ 11:00am*

Where:           * TTIC Conference Room #526*, 6045 S Kenwood Ave, 5th Floor


Who:              * **Brian Y. Chen*, Dept. of Biochemistry and Molecular
Biophysics, Columbia University


Title:          *      **Volumetric Dissection of Protein Functional Sites**
*



 Living things are composed of interacting and nested systems that exhibit
symptoms of health and disease at all levels.  At the most fundamental
level, understanding the correct behavior of healthy systems, and resolving
the breakdowns that occur in disease, requires a precise understanding of
how proteins function and malfunction.  Building such an understanding is
much like the examination of a complex machine: the analysis of protein
shape can yield many insights, especially at functional sites, where
biochemical activity actually occurs.

Many algorithms have been designed to gather structural observations,
especially about the functional site, that point to functional hypotheses
that can be ultimately tested on the bench.  In every case, these methods
employ a "guilt by association" approach by assigning biological function
based on functional site similarity or a resemblance to established norms.
This talk asserts that more informative approaches are possible and presents
VASP, a new method that dissects functional sites to isolate individual
components that play influential functional roles.  VASP enables these new
capabilities by exploiting a novel connection to concepts from computer
graphics and computer aided design.

The results presented in this talk describe a case study where VASP was
applied to the analysis of the major serine proteases.  VASP isolated
individual amino acids and regions of functional sites that enable the
serine proteases to preferentially bind specific molecules.  None of these
observations are possible with existing unsupervised methods.  These results
point to applications in molecular bioengineering, where the identification
of individual functional components is essential for the rational
engineering of active biomolecules, and to applications in structure-based
drug design, where important functional components could be exploited to
mitigate side effects and evade drug resistance.

Host:              Jinbo Xu, j3xu at ttic.edu
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