Dear Howard. Thanks for taking the time to reply. I personally really appreciate it. Moreover, I think others have similar questions as well.

I think we disagree on the need for sampling in protien structure prediction. Also, from what I can tell most of the community agrees with me that current sampling methods are sufficient. It will be interesting and exciting for you to prove all of us wrong!

Also, I wasn't going to bring this up, but since you mentioned it, IMHO your CASP4 results are nice, but not overwhelming. I guess this gets at my original point: is DF going to be the best protein structure prediction method out there? It certainly is going to be the most computationally demanding. After all this computation, if it's not the best (i.e. #1 for many structures, not #2 for one), then is all this really worth it? Is it worth using 100x the resources of everybody else to be #3?

I'm giving you guys a hard time since I think these are questions worth considering. You guys are clearly working hard and doing a great job at running a DC project. The question you should ask yourself is whether the job you're doing is worth doing? Also, it's important to ask how you'll know whether it's worth doing. If you do well, but not spectacularly well at CASP5, doesn't that mean that perhaps you should be putting efforts into methodological aspects, rather than DC (since everyone else, especially those doing better get by w/o DC?)? I feel strongly that there is a "me-too" aspect to DC and people should not be putting efforts into DC projects that are *less successful* than non-DC projects!!!

I'm not saying I know the answer to the "is this worth it" question, but I think it's worth asking and worth knowing how you'll be able to demonstrate that all this (using thousands of people's PC's) is worth it.

I guess you'll say that we might need to wait until CASP5 to see, and I think I've talked enough and don't want to belabor the point. Perhaps it makes sense to revisit this when the CASP5 results are released at the end of the year. Good luck! I hope you prove me (and the rest of the protein structure community) wrong!

Raj