David Baker Staff Lv 1
First of all, I would like to thank all of you for participating in this most exciting new venture! I think FoldIt has real promise for making it possible for people all over the world and from all different backgrounds to bring their talents and unique skill sets to bear on solving critical problems in biomedicine and bioengineering. And of course, have fun at the same time!
My research group at the University of Washington has been working on the protein structure prediction problem for quite some time. With the Rosetta program and the computing power of Rosetta@home, we can now predict structures accurately for small proteins. The main obstacle preventing us from being able to predict structures of larger and more complex proteins is that finding the correct structure becomes increasingly difficult. The correct structure almost always has lower energy than incorrect structures, so if Rosetta can locate the native structure it can be identified based on its very low energy. We find that Rosetta often gets close to the native structure, but not close enough for the energy to drop significantly. This drop requires a last few twists and contortions that Rosetta, which searches by making random changes and evaluating the energy, is not smart enough to try.
The Grand Challenge puzzles are testing whether FoldIt players can overcome these last obstacles which Rosetta often fails at. The starting points in these puzzles are generally pretty close to the correct structure, but there are one or a small number of errors which prevent the energy from dropping (in FoldIt, to get a score more like a traditional computer game, we take the negative of the energy, so a higher score means lower energy).
The exciting preliminary result is that many of you are able to recognize the problems in the starting structures–many of which are the structures that Rosetta trajectories got stuck at==
and fix these problems remarkably well. Over the next month we will be releasing more puzzles with different types of errors in the starting Rosetta generated structures, and doing a full analysis of the results on these challenges which we will report to you directly and to the world via a scientific publication. Beginning with the central issue of whether human intelligence and intuition can overcome obstacles hindering computers from solving problems like protein folding, here are many fascinating questions, most of which have never been considered before.
Keep up the great work!
David