Design of Peptoid Foldamers: Building Beyond the Boundaries of Biology

Abstract

Foldamers are an emerging class of macromolecules, inspired by biopolymers, that fold into well-defined conformations that determine their properties and function. Oligomers of N-substituted glycine, known as peptoids, show promise as foldamers because of the diversity of accessible side chain types and the propensity of certain side chains to promote stable local backbone conformations. Appropriate computational design tools will enable peptoid scientists to search rapidly through chemical and conformational space in search of side chain sequences that stabilize desired backbone conformations.

This dissertation reports new insights into the conformational properties of peptoids that are relevant to designing peptoid foldamers. The work includes a combination of new analysis of previously published structures, and cheminformatic developments that facilitate this analysis; theoretical results from molecular dynamics simulations; experimental results; and proposals for further improvements and new tools in computational design.

The results described herein should enable the design of a new generation of peptoid structures through a combination of computational protocols and expert design. The cheminformatic work that enabled the collection and analysis of all previously published high-resolution peptoid structures is publically available, as are the protocols, scripts, and models developed and used through the course of this work.