Alzheimer's disease (AD), as a human-specific neurodegenerative disorder, is clinically characterized by a progressive decline in cognitive function, such as a reduction in memory abilities, which usually occurs due to some irreversible disordering changes at molecular levels leading to the production of abnormal structures in the brain cells. In several studies, the earliest steps of the disease process have been explored and the accumulation of abnormal amounts of amyloid-beta (Aβ) on extracellular membranes was reported as the primary biological mechanism, which forms amyloid plaques and leads to disturbing neuronal cells operations and their connections in the brain [[1], [2], [3], [4], [5], [6], [7]]. Nguyen et al. have reviewed wide types of experimental and computational research about the accumulation and deposition of the oligomers and proteins, which have been the mainstream concept underlying amyloidogenic diseases such as AD and Parkinson's disease (PD) [5]. One of the major aggregate species in Alzheimer's disease is the amyloid-β (Aβ) peptide, which is a 38–42 amino acid cleavage product of the amyloid precursor protein. Aβ included two charged and hydrophobic domains at the N-terminus and the C-terminus, respectively [6]. Recently, using all-atom molecular dynamics (MD) simulations, the neuronal membrane damage hypothesis has been examined, based on which the formation of complexes between amyloid-β (Aβ) and free lipids enables the insertion of the Aβ peptide into membranes [7]. In some studies, it was reported that amyloid oligomer species are known to have distinct molecular surfaces [8,9]. Sahoo et al. showed that oligomeric species expose their hydrophobic surface and differ from non-toxic fragments, which is a key feature that distinguishes their hypertoxicity and membrane binding. Furthermore, it was found that biological membranes are shown to trap amyloid oligomer intermediates in β-strand conformation that may correlate or differ from matured fibers [10].

In addition, preventing Aβ aggregation on cell membranes seems to be considered one of the most critical AD treatment procedures [11,12]. Hence, finding similar and non-invasive treatments is necessary to overcome the problems and drugs' side effects. In this regard, applying constant radio GHz frequency (RF) electric fields (EF), usually used in communication equipment, could be helpful since RF fields can influence subcellular biological systems due to polar and charged components in their structure. Since the exact mechanism of how the RF fields influence molecular-level interactions between systems' components could be helpful in disease therapy. The effects of such GHz electric fields on the structures and functions of these subcellular bio-systems were considered in several experimental, theoretical, and computational studies [[13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23]]. In a computational study, nonequilibrium MD simulations were performed to examine the effects of application of 1–10 GHz electric fields of strength 0.7, 0.007 and 0.0007 V/nm on an amyloidogenic peptide behavior. The obtained results indicated that specific ranges of EM field parameters produce peptide conformations unfavorable for formation of amyloid fibrils, a phenomenon that can be exploited in treatment and prevention of amyloid diseases. Pomerai et al. found that the bovine serum albumin aggregation depended on time and temperature when the system was exposed to microwave radiation [15]. Another experimental study examined the effects of RF electric fields on human and mouse tumor cell growth. The results confirmed the inhibitory role of the fields on tumor cell growth [16,17]. Computational modeling techniques, such as the MD simulation method, can be beneficial for considering molecular interactions involving protein-protein and protein-lipid interactions when such biological systems are exposed to the RF electric fields. Utilizing these methods, the effects of external electric and magnetic fields on some bio-systems have been investigated, and the structural and functional changes were reported in various systems due to the proteins' responses to applied fields [12,[18], [19], [20], [21], [22], [23], [24]]. For example, the behavior of Fendilin and Diltiazem drug molecules in an L-type calcium channel was explored using the MD simulation method to investigate the influences of GHz electric fields on the drug dynamics in the channel [21]. The results indicated that exposing the channel to such electric fields can affect the effectiveness of such drugs. Lu et al. used atomistic molecular dynamics simulations to study the effects of a constant electric field of 20 mV/nm strength on the conformations of Aβ29–42 dimer inside a membrane [23]. Their reported data indicated that the applied field establishes new ground states for the dimer, similar to induced fit in ligand binding, and showed that exposing the system to such electric fields can stabilize rare conformations of amyloid peptides, and this could influence the formation of β-sheet oligomers in membrane bilayers.

Furthermore, in our previous study [24], the passage of water molecules through an Aquaporin channel was modeled under the application of GHz electric fields, employing the MD simulations method. It was shown that the application of such fields perturbed the expected behavior of the water molecules inside the channel due to the water molecules and the channel charged/polar groups' response to the applied fields. In another computational research, Todorova et al. [25] examined the impacts of 1.0–5.0 GHz electric fields (the field strength between 0.0007 and 0.7 V/nm) on the amyloidogenic peptide dynamics, and they reported that the induced peptide conformations depended on the field frequency and strength.

In this study, we consider and discuss the consequences of the application of the 1 and 5 GHz frequency electric fields on the protein-membrane interactions using the MD simulation method. The amplitude of the applied fields was set at 20 and 70 mV/nm, which is in the range of the membrane resting potential. Our goal is to understand the effects of such fields on Beta-amyloid accumulation on the cell membrane. The outcome of this work provides novel insight into this research field, demonstrating how the applied EF may undermine Beta-amyloid aggregation.