Janet Thornton

The goal of my research is to understand biological processes at the molecular level, by studying protein structures and sequences using computational approaches. Initially as more protein three-dimensional structures were determined, our work involved the collection, description and classification of these beautiful structures and their component motifs, to elucidate the principles governing their folding and evolution. We developed computational tools to compare, validate, analyze and predict structures, leading to a better understanding of the relationship between sequence and structure, and a classification scheme for protein families based on their structures. This includes detailed analyses of the interactions of proteins with other molecules in the cell from a structural perspective with the goal of improving rational drug design. More recently we have focused on functional analysis, exploring how structure determines function and how proteins families evolve to perform novel functions. For example, during evolution many enzymes have been duplicated and evolve to perform new reactions or the same reaction but on different substrates. The structures reveal how this is achieved providing the foundation to understand the mechanisms for the evolution of function. With completed genome sequences, we can extend such studies to consider the evolution of pathways and even organisms.