Banca de QUALIFICAÇÃO: WASHINGTON SALES CLEMENTE JUNIOR

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : WASHINGTON SALES CLEMENTE JUNIOR
DATE: 08/05/2025
TIME: 08:00
LOCAL: Videoconferência - Link para acesso: https://meet.google.com/buu-zman-vmr
TITLE:

Quantum Biochemical Analysis of the Interactions Between the Gamma-Secretase Receptor and Inhibitory Compounds

KEY WORDS:

Alzheimer's disease. Beta amyloid. Gamma secretase. DFT. MFCC.

PAGES: 52
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by the presence of β-amyloid (Aβ) plaques and neurofibrillary tangles, resulting in progressive cognitive decline. Gamma-secretase (GS) plays a central role in Aβ generation, making it a crucial therapeutic target for AD. This study employed advanced molecular modeling methodologies, including molecular docking, molecular dynamics (MD), and calculations based on Density Functional Theory (DFT), to investigate the molecular interactions between the ligands Semagacestat (SEM) and Avagacestat (AVA) and GS. The SEM-GS complex showed higher interaction energy (-46.91 kcal/mol), with significant hydrophobic interactions in region III, involving residues such as LYS380, LEU425, and ALA431. Conversely, the AVA-GS complex highlighted interactions in region II, involving residues like LEU381, LEU425, and ALA434, with an interaction energy of -38.78 kcal/mol. Both ligands demonstrated the importance of hydrophilic and hydrophobic interactions in stabilizing the complexes. The individual energetic contributions of amino acid residues at the binding site were analyzed, identifying key residues that play fundamental roles in the stabilization and selectivity of the protein-ligand complexes.

COMMITTEE MEMBERS:
Interno - 2412258 - EDILSON DANTAS DA SILVA JUNIOR
Presidente - 2985070 - JONAS IVAN NOBRE OLIVEIRA
Externa à Instituição - JÉSSICA DE FÁTIMA VIANNA - UERN