Atomic Coordination Reflects Peptide Immunogenicity

Frontiers in Molecular Biosciences
Georgios S E Antipas, Anastasios E Germenis

Abstract

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 ...Continue Reading

References

Jul 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·P BerozaG Feher
Sep 15, 1988·Physical Review A: General Physics·A D Becke
Jun 23, 2001·Immunity·P A van der Merwe
Mar 5, 2003·Annual Review of Immunology·P Anton van der Merwe, Simon J Davis
Jun 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Dmitry M GakamskyIsrael Pecht
Jul 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shunzhou WanDarren R Flower
Oct 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Wolfgang W A Schamel, Michael Reth
Oct 22, 2009·Chemical Biology & Drug Design·Yuanchao LiQingwu Yang
Apr 17, 2010·Mini Reviews in Medicinal Chemistry·W A Agudelo, M E Patarroyo
Nov 17, 2015·Data in Brief·Georgios S E Antipas, Anastasios E Germenis

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BETA
X-ray

Software Mentioned

Amsterdam density functiona ( ADF )
Amsterdam Density Functional ( ADF )

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