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- Title
Molecular modeling of class I and II alleles of the major histocompatibility complex in Salmo salar.
- Authors
Cárdenas, Constanza; Bidon-Chanal, Axel; Conejeros, Pablo; Arenas, Gloria; Marshall, Sergio; Luque, F.
- Abstract
Knowledge of the 3D structure of the binding groove of major histocompatibility (MHC) molecules, which play a central role in the immune response, is crucial to shed light into the details of peptide recognition and polymorphism. This work reports molecular modeling studies aimed at providing 3D models for two class I and two class II MHC alleles from Salmo salar ( Sasa), as the lack of experimental structures of fish MHC molecules represents a serious limitation to understand the specific preferences for peptide binding. The reliability of the structural models built up using bioinformatic tools was explored by means of molecular dynamics simulations of their complexes with representative peptides, and the energetics of the MHC-peptide interaction was determined by combining molecular mechanics interaction energies and implicit continuum solvation calculations. The structural models revealed the occurrence of notable differences in the nature of residues at specific positions in the binding groove not only between human and Sasa MHC proteins, but also between different Sasa alleles. Those differences lead to distinct trends in the structural features that mediate the binding of peptides to both class I and II MHC molecules, which are qualitatively reflected in the relative binding affinities. Overall, the structural models presented here are a valuable starting point to explore the interactions between MHC receptors and pathogen-specific interactions and to design vaccines against viral pathogens.
- Subjects
MOLECULAR dynamics; MAJOR histocompatibility complex; IMMUNOLOGICAL tolerance; HISTOCOMPATIBILITY; TRANSPLANTATION immunology; HLA histocompatibility antigens; IMMUNOGENETICS; ATLANTIC salmon
- Publication
Journal of Computer-Aided Molecular Design, 2010, Vol 24, Issue 12, p1035
- ISSN
0920-654X
- Publication type
Article
- DOI
10.1007/s10822-010-9387-8