Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Poster Abstracts

18-POS Board 18 NANOMECHANICS OF ANTIBODY AND NANOBODY BINDING TO SARS-COV-2 VARIANTS USING THE G Ō MARTINI 3 APPROACH Adolfo B. Poma 1 ; Luis F. Cofas-Vargas 2 ; Gustavo E. Olivos-Ramirez 1 ; Siewert J. Marrink 3 ; 1 Institute of Fundamental Technological Research of the Polish Academy of Sciences, Biosystems and Soft Matter Division, Warsaw, Poland 2 Universidad Autónoma Metropolitana-Iztapalapa, Departamento de Química, Ciudad de México, Mexico 3 University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, Groningen, The Netherlands The G ō Martini 3 approach [1], enhanced with high-frequency contact maps [2], incorporates dynamic protein contact networks derived from atomistic molecular dynamics. It enables efficient exploration of the conformational landscape and long-time dynamics in large biomolecular systems. This framework is particularly useful for studying host–pathogen interactions and has been applied to uncover the dynamic motions of key domains in the SARS CoV-2 spike (S) protein ectodomain as well as the nanomechanics of a potent nanobody [3].Using this approach, we perform a comparative nanomechanical analysis of SARS-CoV-2 variants (WT, BA.4, JN.1) in complex with three antibodies (PDI-231, S2X259, R1-32) and three nanobodies (R14, C1, n3113.1). Our simulations show that antibody complexes resist mechanical forces through asymmetric rupture pathways, where the heavy chain dominates force transmission while the light chain provides secondary stabilization. In contrast, nanobodies dissociate via rigid-body unbinding with direct force propagation. In both systems, S protein regions 438–507 and 516–529 emerge as recurrent mechanical weak points shaped by variant mutations [4].Overall, we show that mechanical stability in viral protein complexes complements binding affinity in describing immune recognition and provides design principles for more resilient antibody therapeutics against evolving viral variants.References[1] P. Souza, et al., Nat. Commun., 16, 4051 (2025). [2] G. E. Olivos-Ramirez, L. F. Cofas-Vargas, S. J. Marrink, A. B. Poma, An optimized contact map for G ō Martini 3 enabling conformational changes in protein assemblies, Biophys. J. (in press).[3] L. F. Cofas-Vargas, G. E. Olivos-Ramirez, M. Chwastyk, R. A. Moreira, J. L. Baker, S. J. Marrink, A. B. Poma, Nanoscale, 16, 18824–18834 (2024).[4] L. F. Cofas-Vargas, G. E. Olivos-Ramirez, S. J. Marrink, A. B. Poma, Phys. Chem. Chem. Phys., 28, 9159–9171 (2026).

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