Dear Modellers.
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
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Thomas Blicher, Department of Chemistry,
Universitetsparken 5, Copenhagen University, 2100 Copenhagen Denmark.
phone: 45-35320280, fax: 45-35320299
E-mail: thomas(a)kage.ki.ku.dk
