Quantum Chemical Calculations Predict Biological Function: the Case of T Cell Receptor Interaction with a Peptide/MHC Class I

Overview

Journal Front Chem

Specialty Chemistry

Date 2015 Feb 26

PMID 25713797

Citations 7

Authors

Georgios S E Antipas

Anastasios E Germenis

Affiliations

Soon will be listed here.

Abstract

A combination of atomic correlation statistics and quantum chemical calculations are shown to predict biological function. In the present study, various antigenic peptide-Major Histocompatibility Complex (pMHC) ligands with near-identical stereochemistries, in complexation with the same T cell receptor (TCR), were found to consistently induce distinctly different quantum chemical behavior, directly dependent on the peptide's electron spin density and intrinsically expressed by the protonation state of the peptide's N-terminus. Furthermore, the cumulative coordination difference of any variant in respect to the native peptide was found to accurately reflect peptide biological function and immerges as the physical observable which is directly related to the immunological end-effect of pMHC-TCR interaction.

Citing Articles

System-agnostic prediction of pharmaceutical excipient miscibility via computing-as-a-service and experimental validation.

Antipas G, Reul R, Voges K, Kyeremateng S, Ntallis N, Karalis K Sci Rep. 2024; 14(1):15106.

PMID: 38956156 PMC: 11219749. DOI: 10.1038/s41598-024-65978-2.

Quantum vaccinomics platforms to advance in vaccinology.

de la Fuente J, Contreras M Front Immunol. 2023; 14:1172734.

PMID: 37398646 PMC: 10307952. DOI: 10.3389/fimmu.2023.1172734.

A Chirality-Based Quantum Leap.

Aiello C, Abendroth J, Abbas M, Afanasev A, Agarwal S, Banerjee A ACS Nano. 2022; 16(4):4989-5035.

PMID: 35318848 PMC: 9278663. DOI: 10.1021/acsnano.1c01347.

A Quantum Vaccinomics Approach Based on Protein-Protein Interactions.

Contreras M, Artigas-Jeronimo S, Pastor Comin J, de la Fuente J Methods Mol Biol. 2021; 2411:287-305.

PMID: 34816412 DOI: 10.1007/978-1-0716-1888-2_17.

Human Cytomegalovirus variant peptides adapt by decreasing their total coordination upon binding to a T cell receptor.

Antipas G, Germenis A Data Brief. 2016; 4:492-9.

PMID: 26958591 PMC: 4773413. DOI: 10.1016/j.dib.2015.07.019.

References

Cohn M, Mitchison N, Paul W, Silverstein A, Talmage D, Weigert M . Reflections on the clonal-selection theory. Nat Rev Immunol. 2007; 7(10):823-30. DOI: 10.1038/nri2177. View

Ding Y, Baker B, Garboczi D, Biddison W, Wiley D . Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical. Immunity. 1999; 11(1):45-56. DOI: 10.1016/s1074-7613(00)80080-1. View

Agudelo W, Patarroyo M . Quantum chemical analysis of MHC-peptide interactions for vaccine design. Mini Rev Med Chem. 2010; 10(8):746-58. PMC: 3182080. DOI: 10.2174/138955710791572488. View

Cohn M . An in depth analysis of the concept of "polyspecificity" assumed to characterize TCR/BCR recognition. Immunol Res. 2008; 40(2):128-47. PMC: 2892925. DOI: 10.1007/s12026-007-8003-z. View

Wan S, Flower D, Coveney P . Toward an atomistic understanding of the immune synapse: large-scale molecular dynamics simulation of a membrane-embedded TCR-pMHC-CD4 complex. Mol Immunol. 2007; 45(5):1221-30. DOI: 10.1016/j.molimm.2007.09.022. View

Lee , Yang , PARR . Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter. 1988; 37(2):785-789. DOI: 10.1103/physrevb.37.785. View

Sundaram R, Sun Y, Walker C, Lemonnier F, Jacobson S, Kaumaya P . A novel multivalent human CTL peptide construct elicits robust cellular immune responses in HLA-A*0201 transgenic mice: implications for HTLV-1 vaccine design. Vaccine. 2003; 21(21-22):2767-81. DOI: 10.1016/s0264-410x(03)00179-8. View

Wooldridge L, Ekeruche-Makinde J, van den Berg H, Skowera A, Miles J, Tan M . A single autoimmune T cell receptor recognizes more than a million different peptides. J Biol Chem. 2011; 287(2):1168-77. PMC: 3256900. DOI: 10.1074/jbc.M111.289488. View

Pique C, Ureta-Vidal A, Gessain A, Chancerel B, Gout O, Tamouza R . Evidence for the chronic in vivo production of human T cell leukemia virus type I Rof and Tof proteins from cytotoxic T lymphocytes directed against viral peptides. J Exp Med. 2000; 191(3):567-72. PMC: 2195825. DOI: 10.1084/jem.191.3.567. View

10.

Gakamsky D, Luescher I, Pecht I . T cell receptor-ligand interactions: a conformational preequilibrium or an induced fit. Proc Natl Acad Sci U S A. 2004; 101(24):9063-6. PMC: 428473. DOI: 10.1073/pnas.0402840101. View

11.

Fonseca Guerra C, Handgraaf J, Baerends E, Bickelhaupt F . Voronoi deformation density (VDD) charges: Assessment of the Mulliken, Bader, Hirshfeld, Weinhold, and VDD methods for charge analysis. J Comput Chem. 2003; 25(2):189-210. DOI: 10.1002/jcc.10351. View

12.

Wan S, Coveney P, Flower D . Molecular basis of peptide recognition by the TCR: affinity differences calculated using large scale computing. J Immunol. 2005; 175(3):1715-23. DOI: 10.4049/jimmunol.175.3.1715. View

13.

Baker B, Gagnon S, Biddison W, Wiley D . Conversion of a T cell antagonist into an agonist by repairing a defect in the TCR/peptide/MHC interface: implications for TCR signaling. Immunity. 2000; 13(4):475-84. DOI: 10.1016/s1074-7613(00)00047-9. View

14.

Schamel W, Reth M . The TCR binding site does move. Proc Natl Acad Sci U S A. 2007; 104(42):16398-9. PMC: 2034258. DOI: 10.1073/pnas.0708462104. View

15.

Kannagi M, Harada S, Maruyama I, Inoko H, Igarashi H, Kuwashima G . Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells. Int Immunol. 1991; 3(8):761-7. DOI: 10.1093/intimm/3.8.761. View

16.

Becke . Density-functional exchange-energy approximation with correct asymptotic behavior. Phys Rev A Gen Phys. 1988; 38(6):3098-3100. DOI: 10.1103/physreva.38.3098. View

17.

Elovaara I, Koenig S, Brewah A, Woods R, LEHKY T, Jacobson S . High human T cell lymphotropic virus type 1 (HTLV-1)-specific precursor cytotoxic T lymphocyte frequencies in patients with HTLV-1-associated neurological disease. J Exp Med. 1993; 177(6):1567-73. PMC: 2191033. DOI: 10.1084/jem.177.6.1567. View

18.

Donermeyer D, Weber K, Kranz D, Allen P . The study of high-affinity TCRs reveals duality in T cell recognition of antigen: specificity and degeneracy. J Immunol. 2006; 177(10):6911-9. DOI: 10.4049/jimmunol.177.10.6911. View