John Karanicolas, Assistant Professor

Department of Molecular Biosciences

& Center for Bioinformatics

University of Kansas

Designing chemical tools to modulate protein function

Recent years have led to considerable advances in computational protein design, but design or discovery of new protein/small-molecule interactions from scratch remains a challenging unsolved problem. I will describe three short vignettes, each of which tackle this problem in a different way. The first entails building de novo small-molecule binding sites that induce protein activation, to build new classes of switches and sensors. The second involves designing inhibitors of protein-RNA interactions by structural mimicry. The third entails using new metrics of shape complementarity to identify small molecules that bind to shallow grooves on protein surfaces, leading to new inhibitors of protein-protein interactions. Collectively, these different approaches represent a suite of complementary strategies for modulating protein function with small molecules.