Banca de QUALIFICAÇÃO: ALINE DE OLIVEIRA BRAGA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : ALINE DE OLIVEIRA BRAGA
DATE: 17/10/2024
TIME: 09:00
LOCAL: Google Meet
TITLE:

In silico analysis of interactions between halogenated dopamines and the DRD2 receptor

KEY WORDS:

Molecular Dynamics; DFT; Parkinson; MFCC; dopamine Receptors. Molecular Docking

 

PAGES: 31
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Parkinson's disease ranks second among the most common degenerative diseases, with a global prevalence of more than 6 million individuals, and projections that exceed 30 million by 2030. The most common therapeutic option currently is a drug called levodopa, which has proven efficacy in treating symptoms, but has several limitations regarding bioavailability and stability, in addition to presenting adverse effects that raise questions about its use. As an alternative, this study proposes to analyze how altered dopamines - replacement of a hydrogen by halogens (Bromine, Chlorine and Fluorine) - behave in relation to affinity, energy and interactions with the dopamine 2 receptor. Halogens have the ability to form halogen bonds with other macromolecules, which appears to directly influence the pharmacokinetic properties, positively impacting the bioavailability, solubility and ADME of the drug. Understanding how these halogenated dopamine molecules behave with the receptor as well as information about energy, affinities and the demonstration of the dynamics of these complexes can clarify aspects necessary for the design of new, more efficient drugs. In this study, dopamine molecules were altered, and subjected to molecular docking and molecular dynamics (MD) simulations, and subsequently to hybrid calculations (QM/MM) and quantum mechanical calculations to investigate the binding modes and affinities of the four ligands. of DRD2 receptors: DOP (Control), DOPB (Bromine), DOPC (Chlorine) and DOPF (fluorine). The results obtained so far through the VINA score indicate an increase in the affinity of the ligand for the receptor with the introduction of halogens to the structure, we can observe through the data in kcal/mol on the energy of the coupling between ligand and receptor, DRD2-DOPB varied from -178,057 kcal/mol to -246,458 kcal/mol, for DRD2 - DOPC the scores range from -185,633 kcal/mol to -201,317 kcal/mol and for DRD2 - DOPF -187,492 kcal/mol to -229,386 kcal/mol. This study aims to improve knowledge about the interactions between dopamine receptors and ligands and offer the elucidation of new paths in the treatment of neurodegenerative diseases such as Parkinson's disease.

COMMITTEE MEMBERS:
Interno - 2985070 - JONAS IVAN NOBRE OLIVEIRA
Externa à Instituição - KATYANNA SALES BEZERRA - UNICAMP
Presidente - 1352009 - UMBERTO LAINO FULCO