Top7

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Top7 is an artificial protein designed from scratch, a de novo protein. It was created by Brian Kuhlman and Gautam Dantas in David Baker’s lab at the University of Washington.

Top7 is 93 amino acids long and has a mixed alpha/beta structure: two alpha helices packed against a five-stranded anti-parallel beta sheet. This gives Top7 a unique three-dimensional shape.

To design Top7, researchers used computer methods to plan the sequence and predict the structure. They started with a two-dimensional diagram of constraints and built a 3D model from it. The designed protein was then built and tested experimentally.

The high-resolution X-ray structure (PDB 1QYS) closely matches the computer design, with a very small difference (about 1.2 Å RMSD).

Biophysical studies show Top7 is monomeric and highly soluble. It is very stable, but its folding is not a simple, single-step process (non-cooperative folding). Temperature can cause unfolding, and the protein can exhibit cold denaturation. Some mutations at the ends of the sequence suggest that cooperative folding could occur in a different design.

Top7 demonstrates how computer design can create proteins with specific shapes and properties, offering a platform for making new biomolecules with desired features.

Top7 was highlighted as the RCSB Protein Data Bank’s Molecule of the Month in October 2005, and its core was used in the Rosetta@home logo.