chemistry colloquia

"Palladium-Catalyzed Carbon-Heteroatom Bond-Forming Reactions for the Functionalization of Molecules Big and Small"

Department of Chemistry, MIT

"Augmenting biology through de novo protein design"

Protein design—i.e., the construction of entirely new protein sequences that fold into prescribed structures—has come of age: it is possible now to generate a wide variety stable protein folds from scratch using rational and/or computational approaches. A challenge for the field is to move from what have been largely in vitro exercises to protein design in living cells and, in so doing, to augment biology. This talk will illustrate what is currently possible in this nascent field using de novo -helical coiled-coil peptides as building blocks.1 Coiled coils are bundles of 2 or more  helices that wrap around each other to form rope-like structures. They are one of the dominant structures that direct natural protein-protein interactions. Our understanding of coiled coils provides a strong basis for building new proteins from the bottom up. The first part of this talk will survey this understanding,1 our design methods,2,3 and our current “toolkit” of de novo coiled coils.4-6 Next, I will describe how the toolkit can be used to direct protein-protein interactions and build complex protein assemblies in bacterial cells. First, in collaboration with the Savery lab (Bristol), we have used homo- and hetero-oligomeric coiled coils as modules in engineered and de novo transcriptional activators and repressors.7 Secondly, with the Warren (Kent) and the Verkade (Bristol) labs, we have engineered hybrids of a de novo heterodimer and a natural component of bacterial microcompartments to form a “cytoscaffold” that permeates E. coli cells.8 This can be used to support the co-localisation of functional enzymes. University of Bristol

Chemistry colloquium

Beihang University