Banca de DEFESA: LEONARDO LUIZ DE SENA FERNANDES

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : LEONARDO LUIZ DE SENA FERNANDES
DATE: 15/04/2026
TIME: 09:00
LOCAL: Google Meet
TITLE:

Analysis of the Conservation of Interaction Sites Between Chordate AChE and the Drug Donepezil Using Quantum and Evolutionary Methods.

KEY WORDS:

Acetylcholinesterase; Evolutionary conservation; Molecular modeling.

PAGES: 36
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Acetylcholinesterase (AChE) is a key enzyme in the functioning of the nervous system, responsible for the hydrolysis of the neurotransmitter acetylcholine in the synaptic cleft. Due to its central role in cholinergic neurotransmission, it is an important therapeutic target in the treatment of neurodegenerative diseases such as Alzheimer’s disease. In this study, the evolutionary conservation of the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of the enzyme among chordates was investigated, along with the energetic contributions of residues involved in the interaction with the drug donepezil, considering specifically the enzymes from Tetronarce californica and Homo sapiens. The adopted approach combined sequence conservation analysis, structural modeling — including artificial intelligence-based methods — and quantum mechanical calculations of protein–ligand interaction energies using Density Functional Theory (DFT) within the Molecular Fractionation with Conjugate Caps (MFCC) framework. The results indicate that the functional conservation of AChE is not directly associated with global sequence identity, but rather with the preservation of a highly organized structural and physicochemical microenvironment within the binding sites. Additionally, the protein–ligand interaction profile was found to be modulated by local adjustments, without significant alterations in the overall architecture of the complex. Taken together, these findings highlight the central role of the molecular microenvironment in governing protein–ligand interactions and provide a theoretical basis for the cautious extrapolation of structural data across species, contributing to rational drug design strategies.

COMMITTEE MEMBERS:
Presidente - 1513597 - JOAO PAULO MATOS SANTOS LIMA
Interno - 1893445 - EUZEBIO GUIMARAES BARBOSA
Externo à Instituição - ROOSEVELT ALVES DA SILVA