3 ms·

" If folding time isn't a good measure of forcefield accuracy then I don't know what is." Folding kinetics are surprisingly insensitive to detail. For example,

by timr 13y ago

" If folding time isn't a good measure of forcefield accuracy then I don't know what is." Folding kinetics are surprisingly insensitive to detail. For example, it's been understood for a while that even ridiculously simple models can predict transition state energies for simple proteins: http://www.ncbi.nlm.nih.gov/pubmed/10322214?dopt=Abstract http://www.ncbi.nlm.nih.gov/pubmed/10322214?dopt=Abstract http://www.ncbi.nlm.nih.gov/pubmed/10500172?dopt=Abstract http://www.ncbi.nlm.nih.gov/pubmed/10500172?dopt=Abstract But to answer your question, I'd say that "predicting the correct structure of a protein" is the gold-standard benchmark of forcefield accuracy, and MD forcefields are really bad at it. (You could reasonably add other great measures, like: "does the simulation tend to fly apart without hacked-up pseudo-physical constraints?", but that feels like piling on.)

cing 13y ago
I'm biased since I do simulations but you're being too harsh on force fields. All the proteins in the paper I mentioned had their structure correctly predicted starting from an extended state. Correct structure and folding time! That's a serious accomplishment compared to the decade-old papers you're citing.
- timr 13y ago
  "That's a serious accomplishment compared to the decade-old papers you're citing." What? It's not like the "decade-old" paper has become less correct over time. I mean, it's great that MD is finally close to predicting something that could be predicted a decade ago with much simpler methods, but that isn't saying a lot. Plus, as the other commenter pointed out, there's a complicated cross-validation problem that biases the results you're reporting. In truly blind tests (i.e. CASP), MD force fields just aren't that good at predicting structure from sequence. The usual counter-argument is that they aren't meant to work with non-MD methods (fair enough, I guess), but you don't have to try very hard to find reasons not to trust them. MD simulations have always been very finicky things, requiring lots of manual intervention to get "right".

by timr 13y ago

cing 13y ago

I'm biased since I do simulations but you're being too harsh on force fields. All the proteins in the paper I mentioned had their structure correctly predicted starting from an extended state. Correct structure and folding time! That's a serious accomplishment compared to the decade-old papers you're citing.

timr 13y ago
"That's a serious accomplishment compared to the decade-old papers you're citing." What? It's not like the "decade-old" paper has become less correct over time. I mean, it's great that MD is finally close to predicting something that could be predicted a decade ago with much simpler methods, but that isn't saying a lot. Plus, as the other commenter pointed out, there's a complicated cross-validation problem that biases the results you're reporting. In truly blind tests (i.e. CASP), MD force fields just aren't that good at predicting structure from sequence. The usual counter-argument is that they aren't meant to work with non-MD methods (fair enough, I guess), but you don't have to try very hard to find reasons not to trust them. MD simulations have always been very finicky things, requiring lots of manual intervention to get "right".