Morphology of a Transmembrane Aβ42 Tetramer via REMD Simulations
Chúng tôi vui mừng thông báo rằng TS. Ngô Sơn Tùng và các đồng nghiệp gần đây đã xuất bản công trình của họ có tựa đề "Morphology of a Transmembrane Aβ42 Tetramer via REMD Simulations" trên tạp chí Journal of Chemical Information and Modeling.
The folding/misfolding of membrane-permiable Amyloid beta (Aβ) peptides is likely associated with the advancing stage of Alzheimer’s disease (AD) by disrupting Ca2+ homeostasis. In this context, the aggregation of four transmembrane Aβ17–42 peptides was investigated using temperature replica-exchange molecular dynamics (REMD) simulations. The obtained results indicated that the secondary structure of transmembrane Aβ peptides tends to have different propensities compared to those in solution. Interestingly, the residues favorably forming β-structure were interleaved by residues rigidly adopting turn-structure. A combination of β and turn regions likely forms a pore structure. Six morphologies of 4Aβ were found over the free energy landscape and clustering analyses. Among these, the morphologies include (1) Aβ binding onto the membrane surface and three transmembrane Aβ; (2) three helical and coil transmembrane Aβ; (3) four helical transmembrane Aβ; (4) three helical and one β-hairpin transmembrane Aβ; (5) two helical and two β-strand transmembrane Aβ; and (6) three β-strand and one helical transmembrane Aβ. Although the formation of the β-barrel structure was not observed during the 0.28 ms─long MD simulation, the structure is likely to form when the simulation time is further extended.