|
NISCAIR ONLINE PERIODICALS REPOSITORY (NOPR) >
NISCAIR PUBLICATIONS >
Research Journals >
Indian Journal of Experimental Biology (IJEB) >
IJEB Vol.50 [2012] >
IJEB Vol.50(02) [February 2012] >
| Title: | In silico analysis of peptide binding features of HLA-B*4006 |
| Authors: | Gadewal, Nikhil S
Joshi, Narendra N |
| Keywords: | Binding Free Energy
Docking
HLA-B*4006
Homology-modeling
Promiscuous |
| Issue Date: | Feb-2012 |
| Publisher: | NISCAIR-CSIR, India |
| Abstract: | HLA-B*4006 is the most common allele amongst Indians. It belongs to the
‘HLA-B44 supertype’ family of alleles that constitute an important component of
the peptide binding repertoire in populations world over. Its peptide binding
characteristics remain poorly examined. The amino acid sequence and structural
considerations suggest a small, poorly hydrophobic ‘F’ pocket for this allele
that may adversely affect the interaction with the C terminal residue of the
antigenic peptide. Contribution of auxiliary anchor residues (P3) of the
peptide has also been indicated. To examine these aspects by in silico
analysis, HLA-B*4001, 4002, and 4006 alleles were modeled using HLA-B*4402 as a
template. Eleven peptides, known to bind alleles of this family, were used for
docking and molecular dynamics studies. Interaction between the amino group
(main-chain) of P3 residue and Tyr99 of the alleles was seen in majority of
peptide-complexes. Hydrophobic interactions between Tyr7 and Tyr159 with N
terminal residues of the peptide were also seen in all the complexes.
Replacement of Trp95 by leucine in HLA-B*4006 resulted in reduction of binding free
energy in 8 out of 9 complexes. In summary, the analysis of the modeled
structures and HLA-peptide complexes strongly supports the adverse effect of
Trp95 at pocket F and the possible role of the third residue of the antigenic
peptide as an auxiliary anchor in HLA-B*4006 peptide complexes. In the light of
suggested promiscuous peptide binding pattern and association with risk for
tuberculosis/HIV for this allele, the ascertainment of the predicted effects of
Trp95 and role of P3 residue as an auxiliary anchor by this preliminary in
silico analysis thus helps define direction of the further studies. |
| Page(s): | 93-100 |
| CC License: |  CC Attribution-Noncommercial-No Derivative Works 2.5 India |
| ISSN: | 0975-1009 (Online); 0019-5189 (Print) |
| Source: | IJEB Vol.50(02) [February 2012]
|
|
