Molecular Dynamics and Quantum Machine Learning Model to Classify Polymorphisms in Multiple Sclerosis
Resumo
Multiple Sclerosis is an autoimmune disorder associated with specific HLA-DRB1 alleles however, the structural mechanisms underlying this association remains poorly understood. We developed a model integrating molecular dynamics (MD), machine learning (ML), and quantum neural networks (QNN) to classify alleles as either risk-related or protective. MD simulations of HLA-peptide complexes were conducted, and distance matrices were used as input for a ML-QNN classifier. The combined complex protein (chains A and B) and peptide input resulted in the highest accuracy (0.990) and most stable convergence. This study shows the potential of quantum-classical models in identifying subtle structural patterns linked to autoimmune susceptibility.
Palavras-chave:
structural bioinformatics, quantum-classical models, utoimmune susceptibility
Referências
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Wu EL, Cheng X, Jo S, Rui H, Song KC, Dávila-Contreras EM, Qi Y, Lee J, Monje-Galvan V, Venable RM, Klauda JB, Im W. (2014) “CHARMM-GUI Membrane Builder toward realistic biological membrane simulations”. J Comput Chem. Oct 15;35(27):1997-2004. DOI: 10.1002/jcc.23702. Epub 2014 Aug 7. PMID: 25130509; PMCID: PMC4165794.
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Michaud-Agrawal N, Denning EJ, Woolf TB, Beckstein O. (2011) “MDAnalysis: a toolkit for the analysis of molecular dynamics simulations”. J Comput Chem. Jul 30;32(10):2319-27. DOI: 10.1002/jcc.21787. Epub 2011 Apr 15. PMID: 21500218; PMCID: PMC3144279.
Nourbakhsh B, Mowry EM. (2019) “Multiple Sclerosis Risk Factors and Pathogenesis”. Continuum (Minneap Minn). Jun;25(3):596-610. DOI: 10.1212/CON.0000000000000725.
Hollenbach JA, Oksenberg JR. (2015) “The immunogenetics of multiple sclerosis: A comprehensive review”. J Autoimmun. Nov;64:13-25. DOI: 10.1016/j.jaut.2015.06.010. Epub 2015 Jul 2. PMID: 26142251; PMCID: PMC4687745.
De Silvestri A, Capittini C, Mallucci G, Bergamaschi R, Rebuffi C, Pasi A, Martinetti M, Tinelli C. (2019) “The Involvement of HLA Class II Alleles in Multiple Sclerosis: A Systematic Review with Meta-analysis”. Dis Markers. Nov 6;2019:1409069. DOI: 10.1155/2019/1409069. PMID: 31781296; PMCID: PMC6875418.
Rock KL, Reits E, Neefjes J. (2016) “Present Yourself! By MHC Class I and MHC Class II Molecules”. Trends Immunol. Nov;37(11):724-737. DOI: 10.1016/j.it.2016.08.010. Epub 2016 Sep 7. PMID: 27614798; PMCID: PMC5159193.
Chastain EM, Miller SD. (2012) “Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease”. Immunol Rev. Jan;245(1):227-38. DOI: 10.1111/j.1600-065X.2011.01076.x. PMID: 22168423; PMCID: PMC3586283.
Karnaukhov V, Paes W, Woodhouse IB, Partridge T, Nicastri A, Brackenridge S, Shcherbinin D, Chudakov DM, Zvyagin IV, Ternette N, Koohy H, Borrow P, Shugay M. (2022) “HLA variants have different preferences to present proteins with specific molecular functions which are complemented in frequent haplotypes”. Front Immunol. Dec 20;13:1067463. DOI: 10.3389/fimmu.2022.1067463. PMID: 36605212; PMCID: PMC9808399.
Sali A, Blundell TL. (1993) “Comparative protein modelling by satisfaction of spatial restraints”. J Mol Biol. Dec 5;234(3):779-815. DOI: 10.1006/jmbi.1993.1626. PMID: 8254673.
Wu EL, Cheng X, Jo S, Rui H, Song KC, Dávila-Contreras EM, Qi Y, Lee J, Monje-Galvan V, Venable RM, Klauda JB, Im W. (2014) “CHARMM-GUI Membrane Builder toward realistic biological membrane simulations”. J Comput Chem. Oct 15;35(27):1997-2004. DOI: 10.1002/jcc.23702. Epub 2014 Aug 7. PMID: 25130509; PMCID: PMC4165794.
D. Van Der Spoel, et al., (2005) “GROMACS: Fast, Flexible, and Free”, J Comput Chem, vol. 26, pp. 1701-1718, October.
Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ. (2005) “GROMACS: fast, flexible, and free”. J Comput Chem. Dec;26(16):1701-18. DOI: 10.1002/jcc.20291. PMID: 16211538.
Michaud-Agrawal N, Denning EJ, Woolf TB, Beckstein O. (2011) “MDAnalysis: a toolkit for the analysis of molecular dynamics simulations”. J Comput Chem. Jul 30;32(10):2319-27. DOI: 10.1002/jcc.21787. Epub 2011 Apr 15. PMID: 21500218; PMCID: PMC3144279.
Publicado
29/09/2025
Como Citar
RUEDA, Diego; ALVES, Levy Bueno; FARIA JUNIOR, Milton; GIULIATTI, Silvana.
Molecular Dynamics and Quantum Machine Learning Model to Classify Polymorphisms in Multiple Sclerosis. In: SIMPÓSIO BRASILEIRO DE BIOINFORMÁTICA (BSB), 18. , 2025, Fortaleza/CE.
Anais [...].
Porto Alegre: Sociedade Brasileira de Computação,
2025
.
p. 142-150.
ISSN 2316-1248.
DOI: https://doi.org/10.5753/bsb.2025.15114.
