Banca de DEFESA: EMMANUEL DUARTE BARBOSA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : EMMANUEL DUARTE BARBOSA
DATE: 21/02/2022
TIME: 09:00
LOCAL: https://meet.google.com/xng-tyzv-ktu
TITLE:

Investigation of protein-ligand complexes by methods of quantum biochemistry and molecular evolution

KEY WORDS:

DFT, MFCC, interaction energy, ALAD, PBGS, Lys49-PLA 2 , PCA, Bothrops moojeni, phylogeny

PAGES: 104
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

This thesis presents three studies carried out in the sphere of molecular modeling based on principles of Quantum Mechanics. Additionally, molecular evolution methods complemented some results. The first study portrays the particularities of the performance of the energy and computational cost results of 9 combinations of models based on DFT (DFT -- Density Functional Theory) in an organometallic system formed by the divalent zinc cation and the enzyme Porphobilinogen Synthase PBGS. The interaction energies were obtained using the Fragmentation with Conjugated Caps (MFCC) scheme. The results of the total interaction energy profile showed linear quantitative differences, but were qualitatively uniform. The computational processing time dependency is more associated with the choice of basis set than the exchange and correlation functional. The second study presents a biochemical description from the interaction energy results obtained in the previous study, analyzing the biochemical profile of the most relevant PBGS residues that interact with zinc. In addition, a phylogenetic and cluster analysis was performed that evaluated the conservation of the relevant amino acids identified in the zinc-PBGS system. The most important intermolecular interactions were due to the participation of amino acids CS0122, CIS0124, CIS0132, ASP0169, SER0168, ARG0221, HIS0131, ASP0120, GLY0133, VAL0121, ARG0209, and ARG0174. Among these residues, ASP0120, GLI0133, HIS0131, SER0168, and ARG0209 stood out for occurring in all groups generated by the unsupervised cluster analysis. On the other hand, triple cysteines at 2.5 Å of zinc (CIS0122, CIS0124, and CIS0132) showed the highest attraction energy and are absent in Viridiplantae, Sar, Rhodophyta, and in some groups of Bacteria. The third work presented here investigates the interactions between the Lys49-PLA 2 toxin from the venom of Bothrops moojeni, which causes tissue necrosis in snakebite victims, and two compounds (varespladib, aspirin) with the potential to inhibit the myotoxic activity of these proteins. The methodology utilized here also uses quantum methods based on DFT within the MFCC scheme. From this study, it was possible to predict the relevance of the amino acids that form the Lys49-PLA 2 binding site, among them, we can mention LIS0069, LIS0049, LEU0005, ILE0009, CIS0029, GLI0030, HIS0048, PRO0018, ALA0019, CIS0045, TIR0052, TIR0022, PRO0125*, and FEN0126* which anchor varespladib and residues LIS0069, LIS0049, GLI0032, LEU0002, and LEU0005 which anchor aspirin.

BANKING MEMBERS:
Presidente - 1352009 - UMBERTO LAINO FULCO
Interno - 1513597 - JOAO PAULO MATOS SANTOS LIMA
Externo ao Programa - 6345638 - EUDENILSON LINS DE ALBUQUERQUE
Externo à Instituição - LUIZ ANTONIO RIBEIRO JUNIOR
Externo à Instituição - VALDER NOGUEIRA FREIRE - UFC