Hi Chandrika,
protein structures are clustered into a limited number of energetically favoured stable folds (a few thousand). I.e. proteins adopt the same fold with certain modification if they belong to the same protein family, and even sometimes proteins with different function adopt the same general fold. This is the basic idea of comparative or homology modeling: we can model a wide range of proteins if at least one structure is known from the given fold family. However comparative modeling is not able to model a fold starting form a template that belongs to another fold. In your practical approach probably one of the followings will happen: A., as you move away sequentially in each step from your original template you accumulate more and more errors in your new models. Finally you will have a structure which will have nothing to do neither with the original template nor with the desired new fold. The number of possibilities of new conformations increase exponentially as you are moving away structurally from the original template. Outcome B ., is that finally you will thread a fully diverged sequence (the sequence of the final target) onto a backbone which resembles very much the original template with certain fluctuations at some parts. These are my guesses, the outcome will depend on the comparative modeling program you apply: whether the program copies in a very conservative manner the original backbone of the core or they allow some fluctuations and use optimisation at the end. Modeller is rather the second one.
Andras
Chandrika Mulakala wrote: > > Hi, > > I have question that may sound a little naive. It has more to do with homology > modeling than modeller itself. > Here's the question: > > Since, through homology modeling it is possible to model the structure of a > molecule, given the structure of another molecule that is fairly similar,isn't > it possible theoretically, then, to be able to model the structure of any > protein in that manner? Why isn't it possible to used a modelled structure as > a template for further modelling? > > For example: we could start with an accurate structure of some protein > molecule, change a few residues and then model the mutant. Then use the mutant > as a template, change some more residues and then model it. In this way isn't > it possible, theoretically, to model any protein? What are the practical > problems with this idea? > > Thanks, > Chandrika