Computational design by evolving folds and assemblies over the alphabet in l- and d-α-amino acids

Abstract

A step by step search of polypeptide structure, first for folds over L and D structures, then assemblies over the folds, and finally sequences over the assemblies, by inverse application of the protein alphabet in side chains, is introduced as a practical algorithm for the evolutionary design of biologically-inspired supramolecules tailored to a desired size, shape, and function. With stereochemistry and symmetry as powerful considerations for the design of, respectively, folds and assemblies, two independent octapeptides are accomplished, over the alphabet of L- and D-α-amino acids, as remarkably small Shiga-toxin mimics.