Fulco, Umberto LainoBarbosa, Emmanuel Duarte2022-06-232022-06-232022-02-21BARBOSA, Emmanuel Duarte. Investigação de complexos proteína-ligante por métodos de bioquímica quântica e evolução molecular. 2022. 104f. Tese (Doutorado em Bioinformática) - Instituto Metrópole Digital, Universidade Federal do Rio Grande do Norte, Natal, 2022.https://repositorio.ufrn.br/handle/123456789/48272This thesis presents three researches 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 perfor- mance 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 interac- tion energies were obtained using the Fragmentation with Conjugated Covers (MFCC) scheme. The results of the total interaction energy profile showed linear quantitative diffe- rences, 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 resi- dues, 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-PLA2 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 acti- vity 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-PLA2 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.Acesso AbertoBioinformáticaTeoria do Funcional da Densidade - DFTragmentação Molecular com Capas Conjugada - MFCCPorfobilinogênio síntase - PBGSFospholipase A2 Homóloga - Lys49-PLA2Análise de Componentes Principais - PCAdoctoralThesis