Abstract: Provided herein are human interferon alpha-2 (IFNA2) variants that have decreased or no detectable binding to the human interferon-alpha/beta receptor beta 2 (IFNAR2) as compared to the wild-type human IFNA2 polypeptide. Also provided herein are fusion proteins comprising an antibody or fragment thereof, and a human IFNA2 variant, wherein the IFNA2 variant is covalently linked to the antibody, and wherein the IFNA2 variant has decreased or no detectable binding to the human interferon-alpha/beta receptor beta (IFNAR2) as compared to the wild-type human IFNA2 polypeptide.

Abstract: The present disclosure provides methods for improving libraries for screening protein-protein interactions (PPI) by excluding amino acid substitutions that are predicted to have a redundant or minimal effect on binding between protein binding partners.