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Previous issue date: 2016-03-29 / The guanylate cyclase activator 2B, also known as uroguanylin, is part of the guanylin peptide family, which includes peptides such as guanylin and lymphoguanylin. The guanylin peptides are related to sodium absorption inhibition and water secretion induction. Uroguanylin may be related to various pathologies such as chronic renal failure, congestive heart failure and nephrotic syndrome. Uroguanylin mutations have already been associated with essential hypertension. However, there are no studies on the structural changes in the uroguanylin???s protein that used single nucleotide polymorphisms through the use of molecular dynamics simulations. This study used 16 in silico SNP impact prediction tools to evaluate non synonymous SNPs and to select mutations considered as convergent deleterious, which were further analyzed through long time molecular dynamics simulations of 1 microsecond of duration. The results of the molecular dynamics simulations suggest that all SNPs considered as convergent deleterious suffered some kind of structural change, however, four of these nsSNPs have also undergone flexibility changes, possibly resulting in functional changes. / O ativador guanilato ciclase 2B, tamb??m conhecido como uroguanilina, faz parte da fam??lia de pept??deos da guanilina, a qual inclui pept??deos como a guanilina e a linfoguanilina. Os pept??deos da guanilina est??o ligados ?? inibi????o da absor????o de s??dio e indu????o da secre????o de ??gua. A disfun????o da uroguanilina est?? relacionada ao desenvolvimento de v??rias patologias, como insufici??ncia renal cr??nica, insufici??ncia card??aca congestiva e s??ndrome nefr??tica. Muta????es na uroguanilina tamb??m j?? foram associadas ?? hipertens??o essencial. Entretanto, n??o existem estudos sobre a utiliza????o de simula????es por din??mica molecular para avaliar o impacto estrutural causado por nsSNPs presentes no gene codificador da prote??na uroguanilina. Este estudo utilizou 16 ferramentas in silico de predi????o de impacto de nsSNPs para filtrar nsSNPs convergentes delet??rios para posterior an??lise por simula????es por din??mica molecular de longa dura????o (1 microssegundo de dura????o). Os resultados das simula????es por din??mica molecular sugerem que todos os nsSNPs considerados como convergentes delet??rios sofreram algum tipo de altera????o estrutural, por??m, quatro destes SNPs tamb??m sofreram altera????es de flexibilidade, possivelmente resultando em altera????es funcionais.
| Identifer | oai:union.ndltd.org:IBICT/oai:bdtd.ucb.br:tede/2163 |
| Date | 29 March 2016 |
| Creators | Marcolino, Antonio Carlos Silveira |
| Contributors | Alencar, S??rgio Amorim de |
| Publisher | Universidade Cat??lica de Bras??lia, Programa Strictu Sensu em Ci??ncias Gen??micas e Biotecnologia, UCB, Brasil, Escola de Sa??de e Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UCB, instname:Universidade Católica de Brasília, instacron:UCB |
| Rights | info:eu-repo/semantics/openAccess |
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