Rational design of TNFα binding proteins based on the de novo designed protein DS119.

ABSTRACT: De novo protein design offers templates for engineering tailor-made protein functions and orthogonal protein interaction networks for synthetic biology research. Various computational methods have been developed to introduce functional sites in known protein structures. De novo designed protein scaffolds provide further opportunities for functional protein design. Here we demonstrate the rational design of novel tumor necrosis factor alpha (TNFα) binding proteins using a home-made grafting program AutoMatch. We grafted three key residues from a virus 2L protein to a de novo designed small protein, DS119, with consideration of backbone flexibility. The designed proteins bind to TNFα with micromolar affinities. We further optimized the interface residues with RosettaDesign and significantly

SUBMITTER: Zhu C 

PROVIDER: S-EPMC5079244 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature