Originally posted by Blackout
First, thanks for the reply Howard.
Might there still be a need for ab initio for designing brand new proteins?

"improving" generations. Rather than reduce the 10,000 iterations in gen 0, I was hoping it would be possible to monitor the quality of each protein fold as it is being constructed, and if it becomes worse than the current best fold, then there would be no need to complete it. In other words, I meant interrupting individual folds, not the whole batch of 10,000.

A couple of final, unrelated, questions (there was a sale on questions at the department store and I can't resist a bargain): I've never read any mention that there might be "useless proteins". I was just thinking, creatures evolve and are therefore in a state of flux. Is it fair to say that proteins go through gradual stages on their way to becoming very efficient? Or is it more likely that there are dramatic, random mutations, and presto, there's a nifty new protein in the species. And is it the case that some proteins that were needed by ancestors who are very different from the current creature are still produced, even though their function is no longer needed?

Yours in folding,
Michael Matisko
Good questions.

Yes, ab initio COULD always be useful for protein design, however, usually that is done instead by choosing a fold first, and than exploring 'sequence space', which is a bit more efficient. ab initio could be used to predict effects of mutations though, for example, if it were accurate enough.

I see what you meant for gen 0 now. Since each structure can backtrack while it is being built, we cannot 'end early' if it has a poor score partway through. More to the point, each structure takes less than a second to complete usually, so computing the energy every 10 (or whatever) residues would likely slow things down even if it led to aborted structures, not speed things up. This general issue has come up before. It is better to generate and keep everything, then toss out the garbage rather than try to only generate 'good' structures.

Only about 30-40% (dont quote me on that) of proteins have known or purported functions. The remaining ones may do nothing useful, or we may not have found out what they do yet. Obviously there's no way to know which! IT is very likely that at least some proteins are left over from evolutionary ancestors and are no longer needed. However, many of these will mutate over time, and assuming the mutation isnt harmful (which is unlikely if the protein is useless), the protein will eventually mutate into a non-coding piece of DNA and cease to be transcribed. At this point it will effectively be 'dead'. So probably most transcribed proteins DO have some function.
Generally mutations are very slow and gradual, but I believe there are cases when evolution has been observed to 'accelerate' for no good reason, such as the development of eyes (but again, check a textbook, dont quote me on this).

Hope that clears things up some more, and feel free to share any other ideas you have.