Author's note on the web publication of: "The fold of barstar and the composition of its hydrophobic core"

The work on which this paper is based was carried out from 2000 through 2004. In 2003 I committed to retirement by the end of 2004. At the end, my failure to find a randomized core barstar which could be produced in high yields was disappointing. It seemed to me, however, that the results I had would be of interest to anyone involved in the general problems of protein folding and design. This version was posted on the web on March 12, 2008 after four previous iterations were rejected by various journals. While the original manuscript survived its standard vetting by colleagues at my laboratory and institute, attention to comments by journal referees have improved the final text.

If I had spent all of my last two years looking for better random core barstars, perhaps I would have succeeded. It is always difficult to predict how long a project will take. However, once I had a few clearly active barstars, I spent much of my remaining time on a more ambitious project, the production of a stable protein with a relatively complex fold unlikely to be found in nature. My rather crude design included two copies of the three-stranded beta sheet of barstar and two copies of the long helix of barnase. Using a scheme involving ribosome selection (Hanes J and Pluckthun A, PNAS 94, 4937-4942, 1997) and protease resistance, I got my gene library through one selection cycle with no positive result and never got a second cycle to work. Technical difficulties. C'est la vie. If anyone is interested in picking this up I would be happy to provide details.

RW Hartley

Editors Note: Bob Hartley passed away in 2009.