Physics Colloquium: "Finding Order in Intrinsically Disordered Proteins"

Thursday, October 2, 2014

3:30 PM-4:30 PM

Jeetain Mittal, PhD, Lehigh University

 

Recent findings from extensive bioinformatic studies have challenged the central dogma in structural biology that protein function is directly related to protein structure, which in turn is dictated by the protein sequence—collectively known as protein sequence - structure - function relationships. The so-called intrinsically disordered proteins (IDPs) that do not populate stable structures under physiological conditions, have been identified in a wide variety of organisms. The intrinsic disorder can be at the level of the whole protein or some significantly large segment of the protein thereby rendering these proteins much more flexible than their structured counterpart.

There is significant interest in understanding the physical properties of IDPs due to their functional relevance in diverse biochemical processes such as regulation, signaling, and pathogenesis of several disease conditions. Due to their flexibility and lack of well-defined structure, it is quite challenging to experimentally characterize the details of the heterogeneous structural ensemble of IDPs. In principle, all-atom molecular simulations can provide sufficiently detailed spatiotemporal information on IDP properties. But as highlighted recently in the literature, computer models are unsatisfactory in describing the protein disordered states accurately due to their bias toward protein secondary structures. In this talk, I will describe our recently proposed model (and our philosophy in modifying existing models) that can provide accurate information about IDP behavior without any ad hocassumptions. Results from several different example IDP sequences will be used to demonstrate the usefulness of this model and provide information
on previously unidentified structured motifs in these proteins.
 

Contact Information

Luis Cruz Cruz, associate professor of physics
ccruz@physics.drexel.edu