Submitted by Ricardo Cedraz Duque Moliterno (ricardo.moliterno@uefs.br) on 2017-02-14T00:41:33Z No. of bitstreams: 1 PPGBiotec - Disserta??o corrigida - Isis Bugia.pdf: 6811384 bytes, checksum: 2380cbb790d35324858de90e106415fc (MD5) / Made available in DSpace on 2017-02-14T00:41:33Z (GMT). No. of bitstreams: 1 PPGBiotec - Disserta??o corrigida - Isis Bugia.pdf: 6811384 bytes, checksum: 2380cbb790d35324858de90e106415fc (MD5) Previous issue date: 2016-03-11 / The Visceral Leishmaniasis (VL) is the second most important vector-borne disease in the world, transmitted in the Americas by Lutzomyia longipalpis, vector control is essential for the prevention of the disease. But since it is not possible to identify the oviposition sites, the fight is directed to adult insects, using traps impregnated with chemical attractants. Whereas the Odorant Binding Proteins (OBPs) act in the first level of odor selection, this work used in silico methodology to identify putative vector olfactory chemical modulators based on the structure of OBPs and known ligands. For this, tridimensional (3D) structure of L. longipalpis OBPs were predicted by three comparative modeling methods. The best model, predicted by I-Tasser, was refined by Molecular Dynamics on Gromacs. Then, in a hierarchical virtual screening approach, natural compounds of ZINC12 closer to the typical OBP ligands in global chemical space, provided by ChemGPS-NP, were evaluated and staggered concerning affinity with the orthosteric site from the OBP, by molecular docking on DOCK6. The compounds were scored by GRIDSCORE, then the 100 best classified were submitted to AMBERSCORE, which took into account the flexibility from both OBP and the docked ligands. The lowest energy conformations interacted with a hydrophobic pocket through residues Met6, Gly10, Glu11, Ala9 Arg14, Leu74, Met53, Phe118, Phe119, Pro120, amino groups and formed ionic interaction with carboxyl of Glu11, Furthermore, Phe119, Asn29 and Gln69 formed hydrogen bonds, this last formed donor and acceptor H-bonds. / A Leishmaniose Visceral (LV) ? a segunda doen?a vetorial mais importante do mundo, transmitida nas Am?ricas por Lutzomyia longipalpis, o controle do vetor ? indispens?vel ? preven??o da doen?a. Mas como n?o ? poss?vel identificar onde ocorre a oviposi??o, o combate ? direcionado aos insetos adultos, utilizando armadilhas impregnadas com atrativos qu?micos. Considerando que as Prote?nas Ligadoras de Odor (OBPs) atuam no primeiro n?vel de sele??o dos odores, este trabalho utilizou uma metodologia in silico para identificar potenciais moduladores qu?micos olfativos do vetor baseando-se na estrutura das OBPs e de ligantes conhecidos. Para isso, foram preditas as estruturas tridimensionais (3D) de OBPs de L. longipalpis por tr?s m?todos de modelagem comparativa. O melhor modelo, predito pelo I-Tasser, foi refinado por Din?mica Molecular no Gromacs. Ent?o, numa abordagem hier?rquica da triagem virtual, os compostos naturais do ZINC12 mais pr?ximos dos t?picos ligantes de OBPs no espa?o qu?mico global, fornecido pelo ChemGPS-NP, foram avaliados e escalonados quanto ? afinidade com o s?tio ortost?rico da OBP, pelo acoplamento molecular no DOCK6. Os compostos foram pontuados pelo Gridscore, em seguida, os cem melhores classificados foram submetidos ? pontua??o pelo Amberscore, que levou em conta a flexibilidade tanto da OBP como dos ligantes acoplados. As conforma??es de menor energia interagiram com um bols?o hidrof?bico atrav?s dos res?duos Met6, Ala9, Gly10, Glu11, Arg14, Met53, Leu74, Phe118, Phe119, Pro120; grupamentos amino formaram pontes salinas com a carboxila do Glu11. Al?m disso, os res?duos Phe119, Asn29 e Gln69 formaram liga??es hidrog?nio, sendo que, este ?ltimo res?duo formou liga??es-H aceptoras e doadoras.