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Center for Nonlinear Studies |
The formation of protein complexes is a central element of the function of biological systems at the molecular level. Important biological functions are carried out by multi-protein assemblies that form transiently and are held together by relatively weak pairwise interactions, with dissociation constants often in the micro- to millimolar regime. In my talk, I will describe a simulation model developed specifically to study such weak protein binding on the basis of residue-level coarse-graining and a transferable energy function. With this model, we were able to study protein binding and dissociation at equilibrium, including the formation of both the specific and non-specific complex structures (i.e., transient encounter complexes), as validated by paramagnetic relaxation enhancement NMR experiments.By combining simulations with small-angle X-ray scattering (SAXS) in an ensemble refinement procedure, we could characterize the structures of proteins in solution with intrinsically disordered regions. Results for the ESCRT membrane-protein trafficking system and for protein kinase C highlight the dynamic character and the binding cooperativity in protein assemblies as essential elements of their function.
Host: S. Gnanakaran, 5-1923, ghana@lanl.gov