Investigação in silico da interação de peptídeos antimicrobianos análogos da Stigmurina com modelos de membranas

• Ano de defesa: 2021
• Autor(a) principal: Oliveira, Igor Rafael Resende de
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Rio Grande do Norte; Brasil; UFRN; PROGRAMA DE PÓS-GRADUAÇÃO EM QUÍMICA
• Palavras-chave em Português: Química; Stigmurina; Dinâmica molecular; Peptídeos antimicrobianos
• Link de acesso: https://repositorio.ufrn.br/handle/123456789/47532

Stigmurin (Stig), a peptide originating from the venom of the scorpion Tityus Stigmurus, and its analogs (StigA8 and StigA18), are effective in previous in-vitro and in-vivo studies (Larvae of Mariposa Galleria Mellonella). With Stig showing antibacterial activity on Gram-positive bacteria and the analogs on both Gram-positive and Gram-negative. To investigate in detail the interaction of these peptides with different bacterial membranes and establish structural parameters to discuss the mechanism of action of these peptides, molecular dynamics (DM) simulations of Stig, StigA8, and StigA18 peptides were performed in Gram-positive membrane and Gram-negative membrane models.Systems with 1, 2, and 7 peptides were simulated to investigate the effect of peptide concentration on membrane disturbance. DM simulations were carried out using Groningen Machine for Chemical Simulations (Gromacs) 2018 software package. The perturbation and stability analyzes were performed with MEMPLUG (Membrane Thickness, Area by Lipid and Order Parameter). The intermolecular interaction energies were calculated as a function of the time between each peptide and the membrane, showing that there is a greater stabilization in the interactions of the analog peptides with bacterial membranes compared to Stig. Structural parameters, such as membrane fluidity and lipid area, were also evaluated. Analogous peptides caused greater disorder in the lipid tail of bacterial membranes than Stig, characterizing the greater perturbation effect caused by the analogs. Bacterial membranes underwent a slight increase in their surface area, due to the surface interaction and coupling to the membrane surface by the peptides. Finally, the simulations for the concentrated systems (7 peptides) showed the formation of the aggregates, and consequently, a greater local disturbance on the membranes, with drastic reductions in their thickness at the interaction region. The present work corroborates the experimental results and suggests that the mechanism of action of these peptides must be investigated by longer simulations, in concentrations that favor the formation of the aggregates.