Dresden 2026 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 20: Protein Structure and Dynamics
BP 20.3: Vortrag
Mittwoch, 11. März 2026, 15:30–15:45, BAR/0106
Atomic-Level Insights into Amyloid Resistance Gained from Molecular Dynamics Simulations — •Adrian Felix Schnell1, Tim Moderer2, Marcus Fändrich2, and Nadine Schwierz1 — 1Institute of Physics, Computational Biology, University of Augsburg, Universitätsstraße 1b, 86159 Augsburg, Germany — 2Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany
Systemic AA amyloidosis arises from the misfolding and aggregation of normally soluble serum amyloid A1 (SAA1) protein into pathogenic fibrils. Despite extensive experimental efforts, the molecular driving forces that govern fibril formation and resistance remain only partly understood.
Using atomistic molecular dynamics (MD) simulations of experimentally resolved structures in both the fibrillar and native states, we investigated sequence-specific features that modulate amyloid stability and resistance. Simulations of wild-type SAA1 and two naturally occurring variants known to display amyloid resistance reveal how single-point mutations can markedly influence fibril stability and impede fibril growth. Specifically, the atomistic MD trajectories show that the resistant variants fail to stably adopt the pathogenic fibril conformation, pointing to distinct structural and dynamical mechanisms underlying their protective effect.
Keywords: Protein Misfolding; Molecular Dynamics; Amyloidosis; Amyloid Resistance