Design of a novel globular protein fold with atomic-level accuracy

TitleDesign of a novel globular protein fold with atomic-level accuracy
Publication TypeJournal Article
Year of Publication2003
AuthorsKuhlman, B., Dantas G., Ireton G. C., Varani G., Stoddard B. L., & Baker D.
JournalScience
Volume302
Issue5649
Pagination1364-8
Date Published2003 Nov 21
ISSN1095-9203
KeywordsAlgorithms, Amino Acid Sequence, Circular Dichroism, Computational Biology, Computer Graphics, Computer Simulation, Crystallization, Crystallography, X-Ray, Databases, Protein, Models, Molecular, Molecular Sequence Data, Monte Carlo Method, Nuclear Magnetic Resonance, Biomolecular, Primary Publication, Protein Conformation, Protein Denaturation, Protein Engineering, Protein Folding, Protein Structure, Secondary, Proteins, Software, Solubility, Temperature, Thermodynamics
Abstract

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.

Alternate JournalScience
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