I am trying to model MHC class I molecules and have come across a problem
which appears to be related to the alignment. MHC molecules consist of
three individual peptide chains and I have therefore specified my input
sequence in the alignment file with the chain break character / (see alignment
file below).
When modelled, this gives rise to a model with a serious flaw: It appears
that the chain break character is interpreted by MODELLER as a kind of
"dummy residue". The result is that the first chain is modelled nicely,
but the second and third chains are shifted by one and two residues, respectively.
This is a BIG problem, especially as I am interested in the exact interactions
of the third chain (a small oligopeptide) with the rest of the molecule.
I have come up with a temporary "solution" (hopefully) where I simply
delete the last residue of the first and second chain in order to make
room for the "dummy residue". This produces nice models (which are lacking
two residues), but I would like to be able to model the entire molecule.
This is my alignment file which is modelled by the model.top routine:
>P1;1hhi structureX:1hhi: 1:A : 9:C : MHC I: HLA-A0201: * >P1;1A11 sequence:1A11: 1:A : @:@ : MHC I: HLA-A1101: GSHSMRYFYTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAP WIEQEGPEYWDQETRNVKAQSQTDRVDLGTLRGYYNQSEDGSHTIQIMYG CDVGPDGRFLRGYRQDAYDGKDYIALNEDLRSWTAADMAAQITKRKWEAA HAAEQQRAYLEGRCVEWLRRYLENGKETLQRTDPPKTHMTHHPISDHEAT LRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVP SGEEQRYTCHVQHEGLPKPLTLRWE/ MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKV EHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM /GILGFVFTK
*I've probably forgotten something essential, but I don't see what it is. I would be happy for any comments and suggestions.
Many thanks.
Thomas
--------------------------------------------------------------------------- Thomas Blicher, Department of Chemistry, Universitetsparken 5, Copenhagen University, 2100 Copenhagen Denmark. phone: 45-35320280, fax: 45-35320299 E-mail: