A computational approach for designing D-proteins with non-canonical amino acid optimised binding affinity.

ABSTRACT: Redesigning protein surface topology to improve target binding holds great promise in the search for highly selective therapeutics. While significant binding improvements can be achieved using natural amino acids, the introduction of non-canonical residues vastly increases sequence space and thus the chance to significantly out-compete native partners. The potency of protein inhibitors can be further enhanced by synthesising mirror image, D-amino versions. This renders them non-immunogenic and makes them highly resistant to proteolytic degradation. Current experimental design methods often preclude the use of D-amino acids and non-canonical amino acids for a variety of reasons. To address this, we build an in silico pipeline for D-protein designs featuring non-canonical amino acids. For a

SUBMITTER: Garton M 

PROVIDER: S-EPMC5673230 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature