Raj,

(Yes it is Howard, Brian the Fist is just an alias). You are correct that we are indeed dealing with sampling. But we are NOT using the native structures to help us predict in any way.You are wrong in saying that sampling is not a problem however as it is a very real one.

Most people divide the protein structure prediction problem into 2 distinct parts - sampling and scoring. Sampling is basically answering the question of how does one cleverly explore conformational space to ensure something "native-like" appears in a pool of samples. We are right now addressing that question. Namely, how much can we sample and how good a structure can we get by doing so. We are now at a point where we can reliably say, for an unknown structure, based on its length and secondary structure prediction, what the minimum RMSD will be in a pool of 1 billion samples, for example. Or how much do we need to sample it in order to get a 6A structure, etc. This is a very important question and preictive ability on this can be very powerful.

We have separated sampling from scoring with our method however. Scoring is the second part of the problem, and basically answers the question of how do we choose that one 'best' structure out of the 1 billion, once we've sampled. The fact that we've separated the two problems allows us to use any scoring function(s) or combination thereof, that we choose, after the sampling has been done.

You are correct in saying that in our current 'phase' however, we are not truly predicting structures. I have stated this elsewhere in the past however - we are exploring the sampling problem, and the limits of our sampling algorithm to see if it truly scales up to 1 billion samples (and doesnt just keep sampling a smaller set of structures, that is). From our point of view, it has been highly successful so far, as we have exceeded out previous best samples in all 5 different proteins by 1.5-2 A RMSD by doing these larger samples.

As for CASP 4, please look at Phase II of our 'schedule'. Also, if you took the time to check, you would find that we did indeed participate in CASP4, and attended (but didnt participate) in CASP 3. In CASP 4 we submitted 2 homology modelling predictions (which were amongst the best submitted) and 2 novel folds, one of which was the second best prediction submitted (I believe it was roughly 8A for a 110 residue helical protein).
We hope to submit much more than 4 protein predictions this time around and plan to invest more (human) resources into it this time.

Again, please look through our web site and our publications if you are interested in what we are doing and how it works, it is all explained in gory detail.