Peptide binding to the HLA-DRB1 supertype: a proteochemometrics analysis.
A proteochemometrics approach was applied to a set of 2666 peptides binding to 12 HLA-DRB1 proteins. Sequences of both peptide and protein were described using three z-descriptors. Cross terms accounting for adjacent positions and for every second position in the peptides were included in the models, as well as cross terms for peptide/protein interactions. Models were derived based on combinations of different blocks of variables. These models had moderate goodness of fit, as expressed by r2, which ranged from 0.685 to 0.732; and good cross-validated predictive ability, as expressed by q2, which varied from 0.678 to 0.719. The external predictive ability was tested using a set of 356 HLA-DRB1 binders, which showed an r2(pred) in the range 0.364-0.530. Peptide and protein positions involved in the interactions were analyzed in terms of hydrophobicity, steric bulk and polarity.
Dimitrov
Ivan
I
Faculty of Pharmacy, Medical University of Sofia, 2 Dunav st, 1000 Sofia, Bulgaria.
Garnev
Panayot
P
Flower
Darren R
DR
Doytchinova
Irini
I
D000595:Amino Acid Sequence; D019295:Computational Biology; D006684:HLA-DR Antigens / Q000737:chemistry / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D016018:Least-Squares Analysis; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D040901:Proteomics; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008024:Ligands; D010455:Peptides