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
Released Data Link
Team
Principal Investigator
Team Members
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