@article {2019|2127,
	title = {C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ Tetramer in Solution: Intensive MD Study.},
	journal = {ACS Omega},
	volume = {4},
	year = {2019},
	month = {2019 Jun 30},
	pages = {11066-11073},
	abstract = {<p>Amyloid beta (Aβ) peptides are characterized as the major factors associated with neuron death in Alzheimer\&$\#$39;s disease, which is listed as the most common form of neurodegeneration. Disordered Aβ peptides are released from proteolysis of the amyloid precursor protein. The Aβ self-assembly process roughly takes place via five steps: disordered forms \&rarr; oligomers \&rarr; photofibrils \&rarr; mature fibrils \&rarr; plaques. Although Aβ fibrils are often observed in patient brains, oligomers were recently indicated to be major neurotoxic elements. In this work, the neurotoxic compound S-shape Aβ tetramer (S4Aβ) was investigated over 10 μs of unbiased MD simulations. In particular, the S4Aβ oligomer adopted a high dynamics structure, resulting in unsuccessful determination of their structures in experiments. The C-terminal was suggested as the possible nucleation of the Aβ aggregation. The sequences 27-35 and 39-40 formed rich β-content, whereas other residues mostly adopted coil structures. The mean value of the β-content over the equilibrium interval is \&sim;42 \&plusmn; 3\%. Furthermore, the dissociation free energy of the S4Aβ peptide was predicted using a biased sampling method. The obtained free energy is Δ = -58.44 kcal/mol which is roughly the same level as the corresponding value of the U-shape Aβ peptide. We anticipate that the obtained S4Aβ structures could be used as targets for AD inhibitor screening over the in silico study.</p>
},
	issn = {2470-1343},
	doi = {10.1021/acsomega.9b00992},
	author = {Tung, Nguyen Thanh and Philippe Derreumaux and Vu, Van V and Nam, Pham Cam and Ngo, Son Tung}
}
