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Structural Characterization and Interactions of Conformationally Heterogeneous States of Biomolecules


EMSL Project ID
35407

Abstract

This proposal seeks computational resources for the application of long-scale and enhanced sampling techniques to characterize the inherently flexible and conformationally highly heterogeneous ensembles of macromolecules at the atomic-level. Conformationally heterogeneous states are better described as ensembles of rapidly interconverting conformations rather than well-defined structures.1 The structural characterization of such a continuum of protein states solely by experimental means is very difficult and requires approaches in which molecular simulations are combined with experimental measurements.2-4 In the present proposal, computational simulations coupled to NMR spectroscopy will be used to investigate the conformational heterogeneity of i. bacterial type III secretion proteins and ii. target sequence-calmodulin (CaM) complexes of relevance to cellular control mechanism and signal transduction processes. The long-term goal of this effort is to investigate how diverse sequences can give rise to similar ensembles of structures, and thus allow specific recognition and binding by a receptor or to a target, and establish conformational transition mechanism that enables this process.

Project Details

Project type
Large-Scale EMSL Research
Start Date
2009-10-01
End Date
2012-09-30
Status
Closed

Team

Principal Investigator

Thereza Soares Da Silva
Institution
Universidade Federal de Pernambuco

Team Members

Diego de Paula Santos
Institution
Universidade Federal de Pernambuco

Gabriel Costa Alverni da Hora
Institution
Universidade Federal de Pernambuco

Michelle Archuleta
Institution
Pacific Northwest National Laboratory

Jason McDermott
Institution
Pacific Northwest National Laboratory

Curt Boschek
Institution
Pacific Northwest National Laboratory

Yijia Xiong
Institution
Western University of Health Sciences

Garry Buchko
Institution
Pacific Northwest National Laboratory

T. Straatsma
Institution
Oak Ridge National Laboratory

Dayle Smith
Institution
Intel Corporation

Thomas Squier
Institution
Western University of Health Sciences

Roberto Lins Neto
Institution
Universidade Federal de Pernambuco

Related Publications

Buchko GW, G Niemann, ES Baker, ME Belov, RD Smith, F Heffron, JN Adkins, and JE McDermott. 2010. "A multi-pronged search for a common structural motif in the secretion signal of Salmonella enterica serovar Typhimurium type III effector proteins." Molecular Biosystems 6(12):2448-2458. doi:10.1039/c0mb00097c