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Previous issue date: 2017-03-14 === Currently, various bacteria can be harmful to human health. Moreover, with continued use of antibiotics and development of resistance by these microorganisms, many infections became worrying, with no effective treatments available generating the need for development of other fighting molecules. In this context, the antimicrobial peptides (AMPs) have been proposed as an alternative in the control of infections caused by resistant microorganisms. Despite the variation in sequence levels, AMPs may present high structural conservation in specific families, especially peptides stabilized by disulfide bonds. Canonically, the identification of PAMs is by exploitation of bioactive natural extracts and subsequent analysis and purification thereof. In the post genomics era, in turn, identifying PAMs could be made from databases using molecular modeling of peptides in direct search. In this work were selected AMPs without structure in PDB, from antimicrobial peptide database (APD) (http://aps.unmc.edu/AP/main.php). The sequences were pre-filtered, being selected two AMPs (myticin B and MiAMP-2b) of classes described with modifications in disulfide bonds pattern arrangement. Additionally, the original bank was submitted to STPs identification. PredSTP was used as an additional evaluation. After prefiltering phases, a new potential STP (CRS4C-2b) with a new hypothetical structural topology was modelled by QUARK and simulated at 300 ns molecular dynamics, maintaining the initial structure. The methodology was then applied to identify PAMs in the Zantedeschia aethiopica transcriptome where two new potential PAMs were found that were predicted to be active by CAMP. Thus, the two methodologies developed here can be successfully applied in the identification of new PAMs and in the analysis of the structural diversity of antimicrobial families. === Atualmente, v??rias bact??rias podem ser prejudiciais ?? sa??de humana. Al??m disso, com o uso cont??nuo de antibi??ticos, e desenvolvimento de resist??ncia por parte desses microrganismos, muitas infec????es se tornaram preocupantes, sem tratamentos eficazes dispon??veis gerando a necessidade de desenvolvimento de outras mol??culas de combate. Nesse ??mbito, os pept??deos antimicrobianos (PAMs) t??m sido propostos como uma alternativa no controle de infec????es causadas por microrganismos resistentes. Apesar da variabilidade nas sequ??ncias, os PAMs podem apresentar grande conserva????o estrutural em fam??lias espec??ficas, principalmente em pept??deos estabilizados por pontes dissulfeto. De forma can??nica, a identifica????o de PAMs se d?? pela explora????o de extratos naturais bioativos e posterior an??lise e purifica????o dos mesmos. Na era p??s-gen??mica, por sua vez, a identifica????o de PAMs pode ser feita a partir de bancos de dados utilizando modelagem molecular na busca direta de pept??deos. Nesse trabalho foram selecionados PAMs sem estrutura no PDB, a partir do banco de dados de pept??deos antimicrobianos (APD) (http://aps.unmc.edu/AP/main.php). Desta forma, as sequ??ncias foram pr??-filtradas, sendo selecionados dois PAMs (miticina B e MiAMP-2b) de classes descritas com varia????o na disposi????o ou padr??o de pontes dissulfeto. Al??m disso, o banco original foi submetido ?? identifica????o de STPs. Para tal, o servidor PredSTP foi utilizado como avalia????o adicional. Ao final das etapas de pr??-filtragem, um novo potencial STP (CRS4C-2b) com uma nova topologia estrutural foi modelado pelo QUARK e simulado em din??mica molecular, mantendo a estrutura inicial. A metodologia foi ent??o aplicada para identifica????o de PAMs no transcriptoma de Zantedeschia aethiopica onde foram encontrados dois novos potenciais PAMs que foram preditos como ativos pelo CAMP. Dessa forma, as duas metodologias desenvolvidas aqui podem ser aplicadas com sucesso na identifica????o de novos PAMs e na an??lise de diversidade estrutural de fam??lias antimicrobianas.
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