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Previous issue date: 2016-10-07 / Essa tese trata de duas pesquisas com diferentes naturezas conceituais no campo da modelagem molecular, por?m baseadas em semelhantes princ?pios te?ricos da f?sica qu?ntica e da qu?mica computacional. No primeiro estudo, as estabilidades dos sistemas ER?-OHT (Receptor ? de Estr?geno-Hidroxitamoxifeno), ER?-RAL (Receptor ? de Estr?geno-Raloxifeno) e Integrina ?v?3-Cilengitide foram determinadas em termos energ?ticos a partir da t?cnica de fracionamento molecular com capuzes conjugados (MFCC) e no escopo da teoria do funcional da densidade (DFT) seguindo o esquema GGA-PBE-Grimme para calcular a intera??o energias dos sistemas estudados. No primeiro estudo, foi poss?vel predizer a relev?ncia individual dos amino?cidos Glu, Asp, Arg, Lys no sistema com o Tamoxifeno e Glu, Asp e Lys com o Raloxifeno. Para isso ser poss?vel, as for?as de atra??o e repuls?o dos res?duos que comp?em os sistemas foram calculadas. Cada um desses res?duos apresentou uma energia de intera??o que variou dependendo da natureza qu?mica da sua cadeia lateral, do ambiente de microsolvata??o que o envolve e dos contatos intermoleculares que estabelece. O estudo pioneiro da estabilidade conformacional em termos energ?ticos de uma regi?o livre de amino?cidos incitar? pesquisas centradas no desenvolvimento e s?ntese de novos antagonistas utilizados no tratamento de diversas patologias comuns na popula??o geral. No segundo estudo, foram determinadas as propriedades energ?ticas do sistema Integrina ?V?3-Cilengitide, cuja estrutura cristalogr?fica apresenta c?tions Mn+2. Observou-se a import?ncias dos amino?cidos Ser, Asp, Leu, Arg, Lys, Ala e Pro na intera?ao da integrina com o fragmento RGD (R: arginina; G: glicina; D: ?cido asp?rtico) do cilengitide. A import?ncia da integrina com o fragmento RGD no mecanismo de ades?o de diversas c?lulas envolvidas nas doen?as cancer?genas e tamb?m na implanta??o embrion?ria permitir? o desenvolvimento de novas terapias impactantes na sobrevida de pacientes portadores de diversas neoplasias e na reprodu??o humana. / This thesis deals with two researches with different conceptual nature in the field of molecular modeling based on similar theoretical principles of quantum physics and computational chemistry. In the first study the stabilities of ER?-OHT (Receptor ? Estrogen co-crystalyzed with Hydroxytamoxifen), ER?-RAL (?-Estrogen Receptor co-crystalyzed with Raloxifene) and integrin ?v?3 co-crystalyzed with cilengitide systems were determined in terms of energy from the Molecular Fractionation Technique Caps Conjugates (MFCC), and the scope of the Density Functional Theory (DFT) following GGA-PBE-Grimme scheme for calculating the interaction energy of the systems studied. In the first study, it was possible to predict the relevance of individual amino acids Glu, Asp, Arg, Lys in the system with Tamoxifen and Glu, Asp and Lys in Raloxifene system. For this to be possible, the attraction and repulsion forces of the residues that comprise the systems were calculated. Each of these residues had an energy of interaction that varied depending on the chemical nature of the side chain, the microsolvation environment that surrounds and intermolecular contacts establishing. The pioneer study of conformational stability in terms of energy of free amino acid region will encourage research focusing on the development and synthesis of new antagonists used in the treatment of several common diseases in the general population. In the second study, we determined the energetic properties of Integrin ?V?3-cilengitide system, whose crystallographic structure has Mn+2 cations. It was noted the importance of amino acids Ser, Asp, Leu, Arg, Lys, Ala and Pro in integrin interaction with the RGD fragment (R: arginine; G: glycine; D: aspartic acid) of cilengitide. The importance of integrin with the RGD fragment in the adhesion mechanism of various cells involved in cancers and in embryo implantation allows the development of new therapies impacting on survival of patients with various forms of neoplasms and in human reproduction.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/22233 |
| Date | 07 October 2016 |
| Creators | Mota, Kyvia Bezerra |
| Contributors | 67196675487, http://lattes.cnpq.br/9579151361576173, Andrade Neto, Valter Ferreira de, 59626305487, http://lattes.cnpq.br/4863082845974813, Gavioli, Elaine Cristina, 97013390968, http://lattes.cnpq.br/1759328747578795, Albuquerque, Eudenilson Lins de, 05011124487, http://lattes.cnpq.br/3594651355252245, Galv?o, Douglas Soares, 27028984400, http://lattes.cnpq.br/9138028556380501, Moura, Francisco Anacleto Barros Fidelis de, 94063168468, http://lattes.cnpq.br/2051616130490628, Fulco, Umberto Laino |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM DESENVOLVIMENTO E INOVA??O TECNOL?GICA EM MEDICAMENTOS, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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