Comment in:

Science. 2003 Nov 21;302(5649):1347-8.

Science. 2004 Jun 11;304(5677):1597-9; author reply 1597-9.

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

Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

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.

PMID: 14631033 [PubMed - indexed for MEDLINE]