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On Tue, Jan 5, 2010 at 9:24 AM, Raja Dey <[log in to unmask]> wrote:

Assuming all the above data are right, which of the following way would give the best model for C?

1.   Building homology model of C with A as template.

2.    Building homology model of B with A as template and then use B as template to build C.

Suppose I used MODELLER for this work where an energy minimization step is involved after threading the query sequence on the template.

I need to know which model for C will be better and why?

(1).  I don't have time to list all of the reasons, but it is a certainty that the dissimilar residues between A and B are not all in the same positions as the dissimilar residues in B and C, and each dissimilar residue is going to result in a less accurate model - so if you model A->B->C, you will be propagating errors.  (There is probably a formal mathematical way to express this - there have been many studies on sequence similarity vs. RMSD.)  If you need to convince yourself further, find three structures with similar sequence identities in the PDB, run the experiment with them, and compare the end result to the actual structures.