Hybrid methods in Structural Biology
Most atomic structures are determined by either X-ray crystallography or NMR spectroscopy. However, many large complexes are intractable using these techniques, due to their size, dynamics and/or membrane embedding. With the recent emergence of cryo-EM, we are seeing an increasing number of reconstructions for such complexes with intermediate (~4 to 8 Å) resolution, which can be used for docking atomic structures for isolated domains or components.
I am interested in developing methodologies to combine various informations such as EM maps, atomic structures of isolated domains, but also symmetry, domain-domain interaction and dynamics, into structural models. The goal will be to obtain a systematic way to obtain refined atomic models of large complexes based on such sparce data.
Wong LH, Sinha S, Bergeron JR, Mellor JC, Giaever G, Flaherty P, Nislow C. Reverse Chemical Genetics: Comprehensive Fitness Profiling Reveals the Spectrum of Drug Target Interactions. PLoS Genetics 2016.
Solomonson M, Setiaputra D, Makepeace KAT, Lameignere E, Petrotchenko EV, Conrady DG, Bergeron JR, Vuckovic M, DiMaio F, Borchers CH, Yip CK, Strynadka NCJ. Structure of EspB from the ESX-1 Type VII Secretion System and Insights into its Export Mechanism. Structure 2015.
Bergeron JR, Worrall LJ, Sgourakis NG, DiMaio F, Pfuetzner RA, Felise HB, Vuckovic M, Yu AC, Miller SI, Baker D, Strynadka NC. A refined model of the prototypical Salmonella SPI-1 T3SS basal body reveals the molecular basis for its assembly. PLoS Pathogens 2013.