Banca de QUALIFICAÇÃO: IGOR RAFAEL RESENDE DE OLIVEIRA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : IGOR RAFAEL RESENDE DE OLIVEIRA
DATE: 30/08/2021
TIME: 14:00
LOCAL: videoconferência
TITLE:

In Silico Investigation of Stigmurin Analog Antimicrobial Peptides with Membrane Models 

KEY WORDS:

Stigmurin, Molecular Dynamics, Antimicrobial Peptides, Membrane Models.

PAGES: 100
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Físico-Química
SPECIALTY: Química Teórica
SUMMARY:

Stigmurin (StigA), a peptide originating from the venom of the scorpion Tityus stigmurus, and its analogs (StigA8, StigA15 and StigA18), are effective in previous in-vitro and in-vivo studies (Larvae of Mariposa Galleria Mellonella), with StigA 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 (MD) simulations of StigA, 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. MD simulations were carried out using Gromacs 2018 software package and 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 StigA. 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 StigA, 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.

BANKING MEMBERS:
Presidente - 1959889 - DAVI SERRADELLA VIEIRA
Interno - 1086214 - ANDERSON DOS REIS ALBUQUERQUE
Interna - 1569526 - RENATA MENDONÇA ARAUJO