Many biological functions are carried out by large and dynamic multi-protein assemblies.  These assemblies often form only transiently and are held together by relatively weak pairwise interactions and by intrinsically disordered linkers.  We developed a coarse-grained simulation model to study such systems on the basis of residue-level coarse-graining, a transferable energy function, and enhanced sampling methods.  In an ensemble refinement procedure, we combined simulations with small-angle X-ray scattering (SAXS), spin-label distance measurements (EPR), single-molecule fluorescence energy transfer (FRET), and paramagnetic relaxation enhancement (PRE) experiments as well as conventional solution NMR.  This combination allowed us not only to validate the simulation approach, but also to obtain detailed representations of the structures and motions in systems ranging from the ESCRT membrane-protein trafficking system to multi-module kinases and kinases in dynamic complexes with phosphatases.  The dynamic character and the binding cooperativity of the protein assemblies emerge as essential elements of their function.

Structure and dynamics of multiprotein assemblies from simulation and experiment

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.