Dear Modellers,

I have three published alignments, and I want to use my models generated by Modeller to qualitatively estimate the goodness of the different alignments.

I have made 100 models of my unknown sequence to the target structure using each of the three alignments.

I then binned the objective energy output from the standard Modeller run (see panel A in attached pdf). I also binned the final C-alpha to C-alpha RMS for the generated models to the known homologous structure (see panel B in attached pdf).

Is it true that the energy function is not the best objective measure because different alignments will have different numbers of constraints (i.e. one alignment may correspond to 100 amino acid pairs, whereas a shifted alignment may only have 98 amino acid pairs between the known and unknown sequences.) Can you easily normalize to account for this?

What is the best way to do this? I would like to say that Alignment 1 below is best but I am hesitant.

Hopefully this question is understandable.

Thank you, Michael

------------------------------------------------------------------------ -------------------------- Michael Grabe, Ph.D. Post-doctoral Fellow Howard Hughes Medical Institute University of California, San Francisco 533 Parnassus Ave. San Francisco, CA 94143 mgrabe@itsa.ucsf.edu tel: ++ 415.476.6585 http://itsa.ucsf.edu/~mgrabe