More amazing FoldIt results and new flu virus challenges
As Zoran described in his last post, you have been making advances on many fronts! I think it is absolutely amazing that in a relatively short time you have solved a protein structure that eluded expert structural biologists for many years, developed new algorithms for protein folding that are on par with the best my group has come up with after many years of working on the problem, and contributed to designing a new enzyme. I’m quite sure the general scientific community will be equally amazed once the manuscripts we are putting together that describe your findings are published. And I’m sure the future will be even more exciting!
I write today to tell you about a remarkable further addition to your list of accomplishments. As Zoran mentioned, FoldIt players increased the activity of a novel designed enzyme previously created in my group by remodeling the protein backbone. A 24 residue stretch of the backbone was completely rebuilt, including a thirteen residue insertion. The crystal structure of the redesigned Diels Alder enzyme with the increased activity was just solved by our collaborators, and is remarkably close to the Foldit design model. This is likely the largest remodeling of a protein structure ever achieved by computer based design with this level of accuracy, and certainly the most dramatic remodeling by design that improves the function of a protein. Amazing!
I also want to introduce an exciting new series of puzzles that could have significant real world applications. As described in a recent article in Science magazine (and in the embedded video and podcast linked below), my research group has recently designed two novel proteins which bind tightly to the key surface protein on the Spanish flu influenza virus and appear to block its function. We are now working to improve these further, with the hope of eventually developing new anti-flu drugs. We will be presenting you with these designed proteins in complex with the flu virus protein, and asking you to create new interactions with the flu protein (to make the designed proteins bind more tightly to the virus), and to redesign these proteins so they recognize the flu surface protein from other pandemic influenza strains (these differ by several amino acid substitutions which weaken the binding of the original designed proteins; we will be asking you to fight against the changing virus by changing the designs appropriately). We will test the designs you come up with to see if they bind to the other strains of the virus. With luck we can together develop leads for drugs which could be used in future flu outbreaks.
Link to paper & podcast: http://www.sciencemag.org/content/332/6031/816
And finally, congratulations again for all of your amazing achievements-you are making invaluable contributions to scientific research!( Posted by David Baker 74 1963 | Fri, 05/27/2011 - 18:41 | 4 comments )