Chemists are now capable of developing synthetic heteropolymer systems that can recapitulate the sequence-structure-function relationships exhibited uniquely by biopolymers. We believe these efforts can be propelled by co-opting protein design algorithms to address the challenge of designing structured abiotic polymers. We will describe an ongoing collaboration between experimental and computational research groups that span two primary objectives:

·      Elucidating the conformational propensities of new peptidomimetic oligomers, nicknamed "foldamers"

·      Applying this understanding to the design of functional foldamers, including therapeutics and catalysts

To support these tasks, we have modified Rosetta, a robust protein design and structure prediction code base, to accommodate both non-canonical side chain and backbone chemistries. Our efforts include overhauls made to Rosetta's backbone representation, rotamer library, kinematics, and scoring procedures that enable the design of a variety of
oligomer types. We will highlight recent breakthroughs in the computation-assisted design of

·      Exotic mini-proteins with novel topologies and side chains

·      Folded "peptoid" oligomers composed of N-substituted glycine monomers

·     Abiotic oligomers that abrogate protein-protein interactions identified as elusive drug targets.