Molecular Dynamics Analysis of $A\beta40$ and $A\beta42$ Peptides and the System $A\beta40$ + $A\beta42$

Confirmation: I have read and agree with the workshop's policy on behalf of myself and my co-authors.

Track: long paper (4–8 pages excluding references)

Keywords: molecular dynamics; alzheimer disease; amyloid

TL;DR: Simulações de dinâmica molecular mostram que Aβ42 é mais compacto e propenso à agregação que Aβ40, enquanto o sistema misto aumenta a instabilidade conformacional sem formar oligômeros tóxicos iniciais.

Abstract: Molecular dynamics simulations (MD) of the $A\beta40$ and $A\beta42$ peptides, and mixed $A\beta40$ + $A\beta42$ system, were performed using the GROMACS package in an aqueous medium containing $\text{Na}^+$ and $\text{Cl}^-$ ions at physiological pH ($7.4$). The mixed system was built by placing both peptides in the same water box to probe their intermolecular interactions and conformational behavior in solution. Analysis of RMSD, RMSF,and radius of gyration ($R_g$) indicates that the $A\beta40$ and $A\beta42$ reach conformational equilibrium in aqueous solution and remain structurally stable throughout the simulation. $A\beta42$ presented a more compact conformation, while the mixed $A\beta40$ + $A\beta42$ system showed higher fluctuations and higher values for RMSD, RMSF and $R_g$. SASA and hydrogen bonding revealed relevant differences between the systems, indicating progressive expansion for $A\beta40$ and gradual compaction for $A\beta42$. The mixed system showed higher structural instability and solvation patterns consistent with combined monomer behavior. The results suggest that the coexistence of $A\beta40$ and $A\beta42$ amplifies conformational instability, which may favor the initial oligomerization associated with neurotoxicity in Alzheimer's Disease.

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Presenter: ~Eveline_Matias_Bezerra1

Format: Maybe: the presenting author will attend in person, contingent on other factors that still need to be determined (e.g., visa, funding).

Funding: Yes, the presenting author of this submission falls under ICLR’s funding aims, and funding would significantly impact their ability to attend the workshop in person.

Submission Number: 68