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Dynamic characterization of HLA-B*44 Alleles: A comparative molecular dynamics simulation study

Paper ID Volume ID Publish Year Pages File Format Full-Text
14909 1361 2016 5 PDF Available
Title
Dynamic characterization of HLA-B*44 Alleles: A comparative molecular dynamics simulation study
Abstract

•A complete study is presented on three peptides bound to three different HLA-B*44 alleles.•Peptide binding stability is found to depend on the peptide for HLA-B*44 alleles.•Asp156Leu polymorphism seems to affect the peptide binding stability of EEYLQAFTY peptide.

Human Leukocyte Antigens (HLA) are highly polymorphic proteins that play a key role in the immune system. HLA molecule is present on the cell membrane of antigen-presenting cells of the immune system and presents short peptides, originating from the proteins of invading pathogens or self-proteins, to the T-cell Receptor (TCR) molecule of the T-cells. In this study, peptide-binding characteristics of HLA-B*44:02, 44:03, 44:05 alleles bound to three nonameric peptides were studied using molecular dynamics simulations. Polymorphisms among these alleles (Asp116Tyr and Asp156Leu) result in major differences in the allele characteristics. While HLA-B*44:02 (Asp116, Asp156) and HLA-B*44:03 (Asp116, Leu156) depend on tapasin for efficient peptide loading, HLA-B*44:05 (Tyr116, Asp156) is tapasin independent. On the other hand, HLA-B*44:02 and HLA-B*44:03 mismatch is closely related to transplant rejection and acute-graft-versus-host disease. In order to understand the dynamic characteristics, the simulation trajectories were analyzed by applying Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) calculations and hydrogen bonding analysis. Binding dynamics of the three HLA-B*44 alleles and peptide sequences are comparatively discussed. In general, peptide binding stability is found to depend on the peptide rather than the allele type for HLA-B*44 alleles.

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Keywords
Molecular dynamics simulations; HLA-B*44 alleles; Tapasin dependency; Peptide stability
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Dynamic characterization of HLA-B*44 Alleles: A comparative molecular dynamics simulation study
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 62, June 2016, Pages 12–16
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us