Liu S, Liu SY, Zhu XL, Liang HH, Cao AN, Chang ZJ, Lai LH*, Nonnatural protein-protein interaction-pair design by key residues grafting, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104 (13), 5330-5335, 2007.

Abstract Protein-protein interface design is one of the most exciting fields in protein science; however, designing nonnatural protein-protein interaction pairs remains difficult. In this article we report a de novo design of a nonnatural protein-protein interaction pair by scanning the Protein Data Bank for suitable scaffold proteins that can be used for grafting key interaction residues and can form stable complexes with the target protein after additional mutations. Using our design algorithm, an unrelated protein, rat PLCdelta(1)-PH (pleckstrin homology domain of phospholipase C-delta1), was successfully designed to bind the human erythropoietin receptor (EPOR) after grafting the key interaction residues of human erythropoietin binding to EPOR. The designed mutants of rat PLCdelta(1)-......