These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
15319-103810400720-2-CE_unmarked_non_Jname.pdf (687.25 kB)

In Silico Probing Ca2+ and Zn2+ Permeable Transmembrane 4Aβ1-42 Barrel

revised on 02.11.2020, 08:41 and posted on 03.11.2020, 07:03 by Son Tung Ngo

Alzheimer’s disease (AD) is known as one of the most popular forms of dementia affecting numerous people worldwide. The Amyloid beta (Aβ) peptides form oligomeric conformations that cause the intracellular Ca2+ and Zn2+ abnormality leading to the death of neuron cells. The failure of AD therapy targeting Aβ oligomers probably caused by misunderstanding the ions transport through transmembrane Aβ (tmAβ) ion-like channel since Aβ oligomers transiently exist in a mixture environment involving various order of Aβ oligomers. The high-resolution of tmAβ peptides are thus unavailable until the date. Fortunately, computational approaches are able to complement the missing experimental structures. The transmembrane 4Aβ1-42 (tm4Aβ1-42) barrel, one of the most neurotoxic elements, was thus predicted in the previous work. Therefore, in this context, the Ca2+/Zn2+ ions transport through the tm4Aβ1-42 barrel was investigated by using the fast pulling of ligand (FPL) and umbrella sampling (US) methods. Good consistent results were obtained implying that Ca2+ ion transport through tm4Aβ1-42 barrel with a lower free energy barrier compared with Zn2+ ion. The obtained results about Ca2+/Zn2+ transport across tm1-42 barrel probably enhances the AD therapy since we can design an inhibitor is able to block the transport.


The work is funded by Vietnam National Foundation for Science & Technology Development (NAFOSTED) under the grant number 104.99-2019.57.


Email Address of Submitting Author


Ton Duc Thang University



ORCID For Submitting Author


Declaration of Conflict of Interest

No Conflict of Interest

Version Notes

Version 01