![]() ![]() For the general biological and bioengineering community, several noncanonical backbones have been incorporated into web applications that allow users to freely and rapidly test the presented protocols ( ). Finally, as an example of a novel design application, we describe the automated design of an oligooxopiperazine that inhibits the p53-MDM2 protein-protein interaction. To illustrate the utility of this approach, we describe the first tests of the ROSETTA molecular mechanics energy function in the context of oligooxopiperazines, using quantum mechanical calculations as comparison points, scanning through backbone and side chain torsion angles for a model peptidomimetic. Furthermore, we provide a general outline for implementation of new backbone types not discussed here. The main purpose of our manuscript is to give a detailed description to current and future developers of how each of these noncanonical backbones was implemented. This work is complementary to prior additions to model noncanonical protein side chains in ROSETTA. Here, we present expansions to the ROSETTA platform that enable structure prediction and design of five non-peptidic oligomer scaffolds (noncanonical backbones), oligooxopiperazines, oligo-peptoids, -peptides, hydrogen bond surrogate helices and oligosaccharides. One critical limitation is the limited set of design tools for identifying oligomer sequences that can adopt desired conformations. Conformationally ordered peptidomimetic oligomers are finding broad applications for molecular recognition and for inhibiting protein-protein interactions. Peptidomimetic oligomers can frequently be synthesized using efficient solid phase synthesis procedures similar to peptide synthesis. Peptidomimetics are classes of molecules that mimic structural and functional attributes of polypeptides. ![]()
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