Banca de QUALIFICAÇÃO: IGOR RAFAEL RESENDE DE OLIVEIRA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : IGOR RAFAEL RESENDE DE OLIVEIRA
DATE: 30/04/2026
TIME: 14:00
LOCAL: Videoconferência
TITLE:

Multitarget investigation of antimicrobial peptides Scorpions: Herpesvirus, Trypanosoma cruzi and Bacterial membranes.

KEY WORDS:

PAMs; molecular dynamics; bacterial membrane; Cruzipain; HSV-1

PAGES: 171
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Físico-Química
SPECIALTY: Química Teórica
SUMMARY:

The increasing rise of microbial resistance, combined with therapeutic limitations in the treatment of neglected parasitic diseases and viral infections, underscores the urgent need for rational strategies aimed at developing new bioactive molecules. Within this context, Stigmurin, TsAP-2, and their analogues—peptides derived from the scorpion Tityus stigmurus—have demonstrated antibacterial activity against Gram-positive bacteria, antiproliferative effects on different cancer cell lines, low cytotoxicity toward human erythrocytes, and trypanocidal activity against Trypanosoma cruzi. In this study, classical molecular dynamics (MD) simulations were employed to investigate the structural behavior and interaction energy profiles of these peptides and their analogues against three distinct biological systems: Gram-positive and Gram-negative bacterial membrane models, the enzyme Cruzipain from Trypanosoma cruzi, and domain II (DII) of glycoprotein B from Herpes simplex virus type 1 (HSV-1). Simulations ranging from 300-450 ns for peptide–membrane systems and 300 ns for peptide–protein complexes were performed, followed by analyses of structural stability (RMSD), residue-level conformational fluctuations (RMSF), secondary structure variation, and calculations of total and per-residue interaction potential energy (IPE). In membrane systems, the peptides exhibiting the highest experimental activity showed greater conformational stability and more favorable interaction energies, associated with partial maintenance of α-helical structure and the induction of localized perturbations in membrane thickness. Lipid composition differences between Gram-positive and Gram-negative models significantly influenced the electrostatic and hydrophobic interaction patterns. In peptide–protein systems, the results revealed stabilization of the peptides near the catalytic region, with relevant energetic contributions from cationic residues forming electrostatic interactions with anionic regions of the enzyme. Computational findings were consistent with in vitro and in vivo experimental data, in which peptides displaying lower minimum inhibitory and bactericidal concentrations also exhibited more favorable in silico interaction profiles. Together, these results reinforce the predictive value of molecular dynamics simulations in the rational screening and optimization of bioactive peptides. This integrated approach advances the understanding of how structural properties and interaction energetic relate to biological activity, offering a foundation for the development of peptide-based therapeutic candidates.

COMMITTEE MEMBERS:
Presidente - 1959889 - DAVI SERRADELLA VIEIRA
Externo ao Programa - 1544647 - MATHEUS DE FREITAS FERNANDES PEDROSA - nullInterno - 1859346 - MIGUEL ANGELO FONSECA DE SOUZA