Date of Publication

8-2025

Document Type

Bachelor's Thesis

Degree Name

Bachelor of Science in Biochemistry

Subject Categories

Biochemistry

College

College of Science

Department/Unit

Chemistry

Thesis Advisor

Searle Aichelle S. Duay

Defense Panel Member

Nancy Lazaro-Llanos
Stephani Joy Y. Macalino

Abstract/Summary

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-beta (Aβ) plaques, which results from the aggregation of Aβ42 peptides into oligomers and fibrils. Current therapeutic strategies aim to inhibit or disaggregate these toxic aggregates. Oligomeric states of Aβ42 were previously regarded to exhibit a higher binding affinity with LL-37. This study investigates the potential of the antimicrobial peptide LL-37 as a natural inhibitor of Aβ42 aggregation and fibril formation through in silico analysis. The proponents of this study examined the interactions between LL-37 and Aβ42 oligomers using molecular dynamics simulations, focusing on the pentameric (2BEG) and nonameric (5OQV) forms of Aβ42. The study majorly aimed to assess the binding mechanisms of LL-37 and its effectiveness in inhibiting early-stage aggregation. Four initial systems were subjected to molecular dynamics simulations: a pair of 2BEG oligomers, a pair of 5OQV oligomers, a 2BEG pair with LL-37, and a 5OQV pair with LL-37. Contact analysis was performed on the resulting trajectories to determine key residues between the Aβ42 oligomers and the LL-37 peptide. This revealed preferential binding of LL-37 to crucial residues such as E22, D23, and F20 of Aβ42 which forms stable electrostatic and hydrophobic interactions predominantly with terminal lysine residues of LL-37. The interactions induced significant stabilization of the complex, and suggest that the peptide may act as a potential inhibitor by occupying key binding sites that would otherwise mediate fibril growth. Secondary structure analysis also revealed extensive flexibility on the terminal residues of the Aβ structures upon incorporation of LL-37 to the system, suggesting the peptide’s ability to divert oligomerization into unstructured aggregates. The resulting trajectory on the pentameric form of Aβ42 was processed further through root-mean-square deviation-based clustering to determine the most representative conformation associated with the aggregated state. LL-37 showed preferential binding to lower-order structures, which predicts a mechanism that hampers the intermediate stage of fibrillation.

Abstract Format

html

Language

English

Format

Electronic

Keywords

Alzheimer's disease; Amyloid beta-protein

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Embargo Period

9-22-2028

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Available for download on Friday, September 22, 2028

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