Avaliação do Uso de Técnicas de MMGBSA na Triagem Virtual de Bibliotecas de Ligantes para o Desenvolvimento de Fármacos contra Leishmania amazonensis e Leishmania chagasi.

Detalhes bibliográficos
Ano de defesa: 2011
Autor(a) principal: Carvalho, Gabriel Aires Urquiza de
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal da Paraí­ba
BR
Química
Programa de Pós-Graduação em Química
UFPB
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://repositorio.ufpb.br/jspui/handle/tede/7046
Resumo: Leishmaniases are a group of diseases caused by protozoans of the Leishmania sp. genus. whose vector are the sandflies. These diseases are characterized by lesions in the skin and mucous tissues which can severely impair and deform the patient, without killing them. Leishmaniases, however, can evolve to more severe forms and attack internal organs, particularly the spleen and liver. In their final stages of progression, leishmaniases can be fatal. The treatment of leishmanioses is carried out mainly with the pentavalent antimonials (remarkably sodium stibogluconate and meglumine antimoniate) as first choice drugs, assisted by other antibiotics (anfothericin B, paromomycin and pentamidine) as second line therapeutic agents. These therapeutical options, however, suffer with a number of problems with severe side effects, high costs, the appearance of parasite resistent strains or any combination of these factors. Because of these facts, we have evaluated methods to estimate the free energy variation of interaction between ligands and medically interesting enzymes (Trypanothione Reductase, Pharnesyl Pyrophosphate Synthase and Dihydro Orotate Dehydrogenase) for which there are no theoretical works in this sense. We have also suggested, based on the method that performed better in the tests, those ligands which seem promising. We have evaluated the possibility of replacing the conventional molecular docking, in studies of virtual screening, with free energy estimation calculations done with the MMGBSA (Molecular Dynamics, Generalized Born, Solvent Accessibility) methodology applied to a single minimzed geometry of the solvated ligand-enzyme complex. The role of computation in graphics boards processors, time economy, accuracy of afinity values and the overall capacity of the methods to point out the good ligands were analysed and discussed.