Motif-Driven Design of Protein-Protein Interfaces.
Protein-protein interfaces regulate many critical processes for cellular function. The ability to accurately control and regulate these molecular interactions is of major interest for biomedical and synthetic biology applications, as well as to address fundamental biological questions. In recent years, computational protein design has emerged as a tool for designing novel protein-protein interactions with functional relevance. Although attractive, these computational tools carry a steep learning curve. In order to make some of these methods more accessible, we present detailed descriptions and examples of ROSETTA computational protocols for the design of functional protein binders using seeded protein interface design. In these protocols, a motif of known structure that interacts with the target site is grafted into a scaffold protein, followed by design of the surrounding interaction surface.
Department of Biochemistry, University of Washington, Seattle, WA, USA.
Daniel-Adriano
DA
Silva
Institute of Bioengineering, Ecole polytechnique fédérale de Lausanne, Lausanne, Switzerland.
Bruno E
BE
Correia
Department of Biochemistry, University of Illinois, 600 S. Matthews, Urbana, IL, 61801, USA. procko@illinois.edu.
Erik
E
Procko
D001665:Binding Sites; D019295:Computational Biology; D030562:Databases, Protein; D020407:Internet; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry*; D012984:Software
D011506:Proteins
Computational protein design; Interface design; Motif grafting; Protein–protein interaction; ROSETTA