please see the message, originally directed towards dr. sali, below.
if anyone has any comments, please send them!
many thanks, doug kojetin
Begin forwarded message:
> Dr. Sali: > > I am a graduate student in the Department of Molecular and Structural > Biochemistry at North Carolina State University. I have a question > more about modeling process itself rather than the program MODELLER. > > I have used your program, MODELLER, to create models of a subfamily of > proteins our lab and collaborators are interested in (total ~ 30). > There are approximately 10 solved structures to the domain of > interest. One of these solved structures (structure A) is in the same > subfamily within the same species of proteins we are modeling (model > A), whereas the other 29 proteins are of unknown solved structure. My > question concerning the use of templates in the modeling process. > > ############## > my main question > ############## > > (if this is confusing, please let me know and i will rephrase) ... > > Would using a solved structure (structure A) to model a protein of > exact sequence (model A) which will be used in a comparison of 29 > other structures with no known structures (and lower 'homology' > compared to that of structure A to model A -- which is 100%) bias > model A? Overall, we are interested in comparing all 30 structures. > This comes mostly from outside comments that our modeled protein does > not look 'exactly' like the solved structure. As one would like it to > look as close as possible to the solved structure, it is a model after > all, and perhaps we just need to be more descriptive in explaining our > results, especially pertaining to this specific model. > > ##################### > how i modeled the proteins > ##################### > > I performed a 'modeling parameter assay' to find the number of > templates to use to model a protein (model B), ranging from 1 to ~8 > templates. In addition, I 'assayed' the amount of refinement to use. > > Overall, I had an assay 'shaped' like a matrix with, for example, > refinement across the top and # of templates going down. I produced 50 > models for each and ran a variety of analyses on the models (including > Ca RMSD to the most homologous protein, ERRAT, PROCHECK, etc) and > computed the average 'value' output from the respective analyses. > > All in all, using four (4) templates and a refinement value of 1 > produced the 'stereochemically best' models. > > I applied the same rationale to another protein of interest (model C), > and the same trends were extrapolated. > > question > --> is this rationale 'acceptable'? or how would you do something > similar? > > Many thanks for your input, and I'm sorry for the long-winded email. > > Douglas Kojetin