Banca de DEFESA: WASHINGTON SALES CLEMENTE JUNIOR

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : WASHINGTON SALES CLEMENTE JUNIOR
DATE: 02/12/2021
TIME: 09:00
LOCAL: online
TITLE:

QUANTUM BIOCHEMICAL EVALUATION OF INTERACTIONS BETWEEN BETA SECRETASE 1 RECEPTOR (BACE1) AND LIGANDS

KEY WORDS:

Alzheimer's disease; Beta amyloid; BACE1; DFT; MFCC.

PAGES: 55
BIG AREA: Ciências Biológicas
AREA: Biofísica
SUMMARY:

Alzheimer's disease (AD) is a progressive multifactorial neurodegenerative disorder, and the main cause of dementia in late adulthood. Several hypotheses were presented based on the numerous probable causes to explain this multifactorial disorder, among them, the hypothesis of the amyloid cascade, which suggests that a deposition of beta amyloid (Aβ) in the brain is the cause of damage in AD. Aβ is a product of the cleavage of the Amyloid Precursor Protein (APP) by the β and γ secretases, when abnormal, it results in an imbalance between the production and clearance of the Aβ peptide, which are deposited in diffuse senile plaques. In recent years, several drugs have been developed to reduce Aβ40 and Aβ42 concentrations, including 4-Butoxy-3-chlorobenzyl imidothiocarbamate and Verubecestat, which have great potential. This work analyzes the main interactions that occur between a Beta secretase 1 (BACE1) and its ligands from the Molecular Fragmentation Method with Conjugated Covers (MFCC), using the DFT (Density Functional Theory), for identification of which amino acid residues contribute to the binding between the drug and its receptor. The results showed the energetic values of each amino acid residue constituting the site of interaction with the ligands under analysis. This evaluation took place within a radius of up to 10.0 Å away from the drugs. The results show that residues ASP93, ASP289, TYR132, SER96, THR293, GLY291, LEU91, ILE179, THR292, TRP176, GLY95, PHE169, GLN134 are important for complex formation with the two drugs. The data found are essential for creating new strategies in the development of drugs that can contribute to improving the quality of life of patients with AD.

BANKING MEMBERS:
Externo à Instituição - ANTONIO DE MACEDO FILHO - UESPI
Interno - 076.114.664-45 - JOSÉ XAVIER DE LIMA NETO
Presidente - 1352009 - UMBERTO LAINO FULCO