Abstract for "ISCG2015: Deep Sequencing Meets Structural Biology,"
Weizmann Institute, on June 7th-11th, 2015
Title: Analysis of Protein Networks
Protein-protein interaction (PPI) networks may be studied through the
lens of both 3-dimensional protein structures as well as the
large-scale genome variation data being generated as part of
next-generation sequencing initiatives. In terms of protein structural
data, I will describe how mapping the structures of protein complexes
onto PPI networks enables the classification of hubs into two distinct
types: multi- and singlish-interface. These two categories exhibit
very distinct properties, especially in terms of the well-known
preferential attachment model of network growth. Secondly, I will
discuss how the integration of alternative conformations with PPI
networks further highlights interesting disparities, with the
permanent multi-interface hubs tending to exhibit a greater degree of
conformational plasticity relative to singlish-interface hubs. In
addition, I will briefly discuss how alternative conformations are
being culled from the PDB to study the significance of sequence
variation in the context of allosteric behavior. I will then discuss
the some of the insights gained by integrating variation data with
these networks (especially when using population-scale sequencing data
from the 1000 Genomes Project). Several well-known results are
recapitulated using this data: greater network centralityis associated
with a greater degree of negative selection, and the proclivity of the
network tends to be under positive selection. Finally, I will show how
this type of data further illuminates aspects of the intricacies of
protein structures and motions.
Integration of protein motions with molecular networks reveals
different mechanisms for permanent and transient interactions.
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