This dissertation is composed of two parts, The first part includes chapters 1-3, which is focused on molecular dynamics (MD) studies of the monomers conformations of amyloid-β (Aβ) peptide. We have made comparison study of wild-type Aβ(10-35), which promoted aggregation in vivo and in vitro, and its well-known aggregation-disrupting mutation F19T. Our result shows the WT peptide has a strong preference to form an E22-K28 loop and a reasonable stability for a strand-loop-strand conformation. The F19T mutant has a significantly lower population of E22-K28 loop and SLS structure, but has a high population of Q15-D23 loop. The simulation of full-length Aβ40 and Aβ42 monomers reveals: First of all, Aβ40 and Aβ42 has globally similar conformation in solution; Furthermore, Aβ42 is structurall...[ Read more ]

This dissertation is composed of two parts, The first part includes chapters 1-3, which is focused on molecular dynamics (MD) studies of the monomers conformations of amyloid-β (Aβ) peptide. We have made comparison study of wild-type Aβ(10-35), which promoted aggregation in vivo and in vitro, and its well-known aggregation-disrupting mutation F19T. Our result shows the WT peptide has a strong preference to form an E22-K28 loop and a reasonable stability for a strand-loop-strand conformation. The F19T mutant has a significantly lower population of E22-K28 loop and SLS structure, but has a high population of Q15-D23 loop. The simulation of full-length Aβ40 and Aβ42 monomers reveals: First of all, Aβ40 and Aβ42 has globally similar conformation in solution; Furthermore, Aβ42 is structurally rigid than Aβ40; At last, the additional two residues in Aβ42 may have specific interactions with CHC and lead to the conformational switch via alpha to beta. These results may be a foundation for the understanding of aggregation mechanism and small molecule inhibition of the aggregation. The second part covers chapter 4, it is combination study of experimental and theoretical results. We have developed quadruplex sensors with nonplanar conformations, in particular, the propeller-shaped tetraphenylethene (TPE) salts with aggregation-induced emission (AIE) characteristics, can be associated with a human telomeric DNA strand in the presence of K+ ions. Computational modeling suggests that the AIE molecule docks on the grooves of the quadruplex surface with the aid of electrostatic attraction.