Interactome based drug discovery and disease-disease relationships
Gaurav Chopra, Purdue Center for Drug Discovery, Purdue University
1 – 2PM
Friday May 27, 2016
We have developed a drug discovery and repurposing platform that analyzes compound-protein structural interaction signatures across multiple proteomes to determine drug behavior, in contrast to traditional single (or few) target approaches. Our platform implements a modeling pipeline that generates an interaction between 3,733 human approved drugs and 48,278 proteins using a hierarchical chem- and bio-informatic fragment-based docking with dynamics protocol (~ 1 billion predicted interactions). We prospectively validated our predictions in vitro and in vivo preclinical studies for more than a dozen indications (immunological, metabolic, infectious and genetic). Our multitargeting results indicate that a large number of protein structures with diverse fold space and a specific polypharmacological interactome is necessary for accurate drug predictions using our proteomic and evolutionary drug discovery and repurposing platform. Our approach is broadly applicable beyond repurposing, enables personalized medicine, and foreshadows a new era of faster drug and target discovery using novel disease-disease connections.