Defensina nsd7 de Nicotiana suaveolens acoplada ao ácido fosfatídico: avaliações sobre o mecanismo molecular através da análise de bioquímica quântica e simulações de dinâmica molecular.

• Ano de defesa: 2018
• Autor(a) principal: Nascimento, Thais Ferreira
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Defensina; Bioquímica quântica; Dinâmica molecular
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/39542

Plant defesins are cationic peptide composed of 45-54 amino acids that play a role in innate immune system. The defensins may play several roles in the plant organism including antibacterial activity, proteinase inhibitory, etc. Interactions with cellular phospholipid membranes are a key component of the antimicrobial peptide mechanism. We calculated the residue-residue−drug interaction energies of NsD7 defensin using quantum methods and molecular dynamics simulation to reveal structural data and molecular mechanisms not exposed in the literature. The input data for the calculations performed in this study was the X-ray crystal structure of plant defensin NsD7 complexed with phospatidic acid (PA) (PDB ID: 5KK4). In this study, the interaction energy between a specific pair of amino acid residues and the ligand was achieved from quantum calculations. Also, we performed a molecular dynamic study to analyze the interaction and the stability of the NsD7 molecules in the presence or absence of the phosphatidic acid. The current strategy has found a few extra residues that show significance on the interaction of NsD7 monomers, beyond those previously mentioned in the literature, such as Lys1, Arg5, Glu6, Arg40, Lys45 and Cys47. On the other hand, the results corroborate with the previously, showing that Lys36:PA and Arg39:PA have high interference in the binding energy of the system. Also, we noticed in our study that the residue Lys4 have low repulsive energy. In the previously study, the Lys4 did not showed interference in the oligomer formation. The molecular dynamics simulation corroborated with experimental data, showing that in the absence of PA, the system is incapable to maintain the system stability. On the other hand, when PA molecule is present in the system, the complex NsD7:PA become stable. The quantum calculations used in this work coupled to MD simulations are capable of describing the energy profile of the system as well as the stability analysis of the system as a whole.