Computational Investigation of Coaggregation and Cross-Seeding between Aβ and hIAPP Underpinning the Cross-Talk in Alzheimer’s Disease and Type 2 Diabetes

Journal of Chemical Information and Modeling, Год журнала: 2024, Номер 64(13), С. 5303 - 5316

Опубликована: Июнь 26, 2024

The coexistence of amyloid-β (Aβ) and human islet amyloid polypeptide (hIAPP) in the brain pancreas is associated with an increased risk Alzheimer's disease (AD) type 2 diabetes (T2D) due to their coaggregation cross-seeding. Despite this, molecular mechanisms underlying interaction remain elusive. Here, we systematically investigated cross-talk between Aβ hIAPP using atomistic discrete dynamics (DMD) simulations. Our results revealed that amyloidogenic core regions both (Aβ

Язык: Английский

---

Computational insights into the aggregation mechanism of human calcitonin

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 294, С. 139520 - 139520

Опубликована: Янв. 5, 2025

Язык: Английский

---

Computational insights into the aggregation mechanism and amyloidogenic core of aortic amyloid medin polypeptide

Colloids and Surfaces B Biointerfaces, Год журнала: 2024, Номер 244, С. 114192 - 114192

Опубликована: Авг. 30, 2024

Язык: Английский

---

Molecular Insights into the Effects of F16L and F19L Substitutions on the Conformation and Aggregation Dynamics of Human Calcitonin

Journal of Chemical Information and Modeling, Год журнала: 2024, Номер 64(11), С. 4500 - 4510

Опубликована: Май 15, 2024

Human calcitonin (hCT) regulates calcium-phosphorus metabolism, but its amyloid aggregation disrupts physiological activity, increases thyroid carcinoma risk, and hampers clinical use for bone-related diseases like osteoporosis Paget's disease. Improving hCT with targeted modifications to mitigate formation while maintaining function holds promise as a strategy. Understanding how each residue in hCT's amyloidogenic core affects structure dynamics is crucial designing effective analogues. Mutants F16L-hCT F19L-hCT, where Phe residues the are replaced Leu nonamyloidogenic salmon calcitonin, showed different kinetics. However, molecular effects of these substitutions still unclear. Here, we systematically investigated folding self-assembly conformational hCT, F16L-hCT, F19L-hCT through multiple long-time scale independent atomistic discrete (DMD) simulations. Our results indicated that monomer primarily assumed unstructured conformations dynamic helices around 4-12 14-21. During self-assembly,

Язык: Английский

---

Computational Exploration of the Self-Aggregation Mechanisms of Phenol-Soluble Modulins β1 and β2 in Staphylococcus aureus Biofilms

Colloids and Surfaces B Biointerfaces, Год журнала: 2025, Номер 248, С. 114498 - 114498

Опубликована: Янв. 5, 2025

Язык: Английский

---

Unraveling the aggregation mechanism and bioactivity of Tyr12 nitrated human calcitonin

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 315, С. 144577 - 144577

Опубликована: Май 22, 2025

Язык: Английский

---