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>> Dear Friends,
>>
>>                         I have a question about judging a homology 
>> model. I have three homologous proteins A, B and C of which only A has 
>> 3D crystal structure available. Their similarities/identities are 
>> given below.
>>
>> Pair-wise alignment      similarity/identity (%)
>>
>> A and B                                   63/49
>>
>> A and C                                   54/39
>>
>> B and C                                   60/46
>>
>> 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?
>>
>> Thanks for your answer…
>>
>> Happy New Year to you all,
>>
>> Raja

Raja,

you should take the alignment of B to A into account when you establish 
the alignment of C to A. In other words, construct a multiple alignment 
first (and use sequences D, E, ... as well if they exist), and only then 
build your homology model.
The reason is that the biggest source of error in a homology model comes 
from misalignment of the target and the model sequence. You want to 
avoid this.

HTH,

Kay