Atomic Coordination Reflects Peptide Immunogenicity
| Autor: | Georgios S. E. Antipas, Anastasios E. Germenis |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Stereochemistry Peptide Protonation Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry 03 medical and health sciences Functional avidity 0302 clinical medicine atomic pair correlation Molecular Biosciences Molecular orbital lcsh:QH301-705.5 Molecular Biology Original Research chemistry.chemical_classification Spin polarization Chemistry pMHC-TCR interaction Immunogenicity Relaxation (NMR) cumulative coordination Charge (physics) atomic cooedination Crystallography 030104 developmental biology lcsh:Biology (General) short range order Metric (mathematics) Structure-Function Relationship 030215 immunology |
| Zdroj: | Frontiers in Molecular Biosciences, Vol 2 (2016) Frontiers in Molecular Biosciences |
| ISSN: | 2296-889X |
| DOI: | 10.3389/fmolb.2015.00077 |
| Popis: | We demonstrated that the immunological identity of variant peptides may be accurately predicted on the basis of atomic coordination of both unprotonated and protonated tertiary structures, provided that the structure of the native peptide (index) is known. The metric which was discovered to account for this discrimination is the coordination difference between the variant and the index; we also showed that increasing coordination difference in respect to the index was correlated to a correspondingly weakening immunological outcome of the variant. Additionally, we established that this metric quickly seizes to operate beyond the peptide scale, e.g., within a coordination shell inclusive of atoms up to a distance of 7 Å away from the peptide or over the entire pMHC-TCR complex. Analysis of molecular orbital interactions for a range of formal charges further revealed that the N-terminus of the agonists was always able to sustain a stable ammonium (NH[Formula: see text]) group which was consistently absent in antagonists. We deem that the presence of NH[Formula: see text] constitutes a secondary observable with a biological consequence, signifying a change in T cell activation. While our analysis of protonated structures relied on the quantum chemical relaxation of the H species, the results were consistent across a wide range of peptide charge and spin polarization conditions. |
| Databáze: | OpenAIRE |
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