Design of a novel globular protein fold with atomic-level accuracy.
A major challenge of computational protein design is the creation of novel proteins with arbitrarily chosen three-dimensional structures. Here, we used a general computational strategy that iterates between sequence design and structure prediction to design a 93-residue alpha/beta protein called Top7 with a novel sequence and topology. Top7 was found experimentally to be folded and extremely stable, and the x-ray crystal structure of Top7 is similar (root mean square deviation equals 1.2 angstroms) to the design model. The ability to design a new protein fold makes possible the exploration of the large regions of the protein universe not yet observed in nature.
Kuhlman
Brian
B
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Dantas
Gautam
G
Ireton
Gregory C
GC
Varani
Gabriele
G
Stoddard
Barry L
BL
Baker
David
D
D000465:Algorithms; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D019295:Computational Biology; D003196:Computer Graphics; D003198:Computer Simulation; D003460:Crystallization; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D011489:Protein Denaturation; D015202:Protein Engineering; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012984:Software; D012995:Solubility; D013696:Temperature; D013816:Thermodynamics
D011506:Proteins