Frequency-Dependent Structural Responses of Amyloid-β Fibrils to Terahertz Pulses: A Nonequilibrium Molecular Dynamics Study
- 1Beijing Institute of Technology
Abstract
The abnormal aggregation of amyloid proteins into fibrils is closely associated with several neurodegenerative diseases, highlighting the importance of developing effective strategies to modulate fibril structural stability. Here, we employed nonequilibrium molecular dynamics(NEMD) simulations to examine the effects of intense terahertz-to-mid-infrared pulses on three amyloid fibrils (2LMP, 2MXU, and 5OQV), focusing on the combined effects of pulse frequency and electric-field strength. Frequency scans from 0.5 to 60 THz in 0.5 THz steps revealed frequency-dependent losses of {beta}-sheet content, with several common response patterns in these fibrils. Comparisons at 2, 23, 33, and 50 THz showed that pulse-induced changes in secondary structure differed from those in high-temperature controls. Hydrogen-bond analysis showed that total hydrogen-bond counts could partially recover even as interchain hydrogen bonds continued to decrease, with distinct responses among representative chain pairs. We therefore propose a two-threshold electric-field framework for fibril disruption: Eth1 describes the onset of structural perturbation, whereas Eth2 indicates persistent structural loss after the pulse. This framework offers a testable approach for characterizing amyloid structural responses to external fields, although the underlying energy-coupling mechanisms, quantitative thresholds, and long-term recovery require further validation. These findings may provide a theoretical basis for exploring external-field-based strategies to modulate protein aggregation.
Related
- Testosterone Regulates Sex-Dependent Immune Responses and Androgen Receptor Expression During Plasmodium berghei ANKA Infection
- Structural basis for the CsrA-dependent modulation of translation initiation by an ancient regulatory protein.
- Structural basis for loop-dependent inhibition by AcrIIC1 anti-CRISPR proteins
- Redox-dependent structural and thermal stability of HMGB1: A thermodynamic analysis
- Structural and kinetic mechanisms of state-dependent potassium channel inhibition
BibTeX
@misc{wang2026frequencydependent,
title = {{Frequency-Dependent Structural Responses of Amyloid-β Fibrils to Terahertz Pulses: A Nonequilibrium Molecular Dynamics Study}},
author = {Y. Wang and J. Dai and X. Peng and Q. Zhao},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.764785},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.764785v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Frequency-Dependent Structural Responses of Amyloid-β Fibrils to Terahertz Pulses: A Nonequilibrium Molecular Dynamics Study
AU - Y. Wang
AU - J. Dai
AU - X. Peng
AU - Q. Zhao
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.764785
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.764785v1
AB - The abnormal aggregation of amyloid proteins into fibrils is closely associated with several neurodegenerative diseases, highlighting the importance of developing effective strategies to modulate fibril structural stability. Here, we employed nonequilibrium molecular dynamics(NEMD) simulations to examine the effects of intense terahertz-to-mid-infrared pulses on three amyloid fibrils (2LMP, 2MXU, and 5OQV), focusing on the combined effects of pulse frequency and electric-field strength. Frequency scans from 0.5 to 60 THz in 0.5 THz steps revealed frequency-dependent losses of {beta}-sheet content, with several common response patterns in these fibrils. Comparisons at 2, 23, 33, and 50 THz showed that pulse-induced changes in secondary structure differed from those in high-temperature controls. Hydrogen-bond analysis showed that total hydrogen-bond counts could partially recover even as interchain hydrogen bonds continued to decrease, with distinct responses among representative chain pairs. We therefore propose a two-threshold electric-field framework for fibril disruption: Eth1 describes the onset of structural perturbation, whereas Eth2 indicates persistent structural loss after the pulse. This framework offers a testable approach for characterizing amyloid structural responses to external fields, although the underlying energy-coupling mechanisms, quantitative thresholds, and long-term recovery require further validation. These findings may provide a theoretical basis for exploring external-field-based strategies to modulate protein aggregation.
ER -