How do antimicrobial peptides destroy membranes? A Molecular Dynamics perspective (2023)
- Authors:
- Autor USP: PARK, PETER - IQ
- Unidade: IQ
- Sigla do Departamento: QBQ
- DOI: 10.11606/T.46.2023.tde-11122023-182928
- Subjects: PEPTÍDEOS; ANTIBIÓTICOS
- Keywords: Antibióticos; Antibiotics; Antimicrobial peptides; Coarse-graining MD; Coarse-graining MD; Dinâmica Molecular; Drug design; Mecanismo de ação; Mechanism of action; Molecular Dynamics; Peptídeos antimicrobianos
- Language: Inglês
- Abstract: Cationic alpha-helical antimicrobial peptides (CHAMP) are potential candidates as novel drugs against resistant bacteria. CHAMPs are short amphipathic, membrane-active peptides in many organisms as part of their innate immune defense system. CHAMPs spark interest in pharmaceutical applications due to their ability to bear less risk of inducing bacterial resistance than conventional antibiotics, selectivity towards bacteria and fungi, and fast antimicrobial action. Their detailed mechanism of action on membranes needs to be clarified. Elucidating CHAMPs' mode of action can provide relevant information that can be used to better design new CHAMPs with higher efficacy and selectivity. Here, we used Molecular Dynamics (MD) simulations to investigate the detailed mode of action of BP100 (H-KKLFKKILKYL-NH2), a promising CHAMP, on membranes. We characterized the initial interaction between a single BP100 and membranes using atomistic simulations. We described peptide flip, a dynamic phenomenon in which BP100 binds to the membranes, rotates and penetrates the membrane core, and causes local membrane effects, such as thinning, negative curvature, and a decrease in lipid lateral diffusion. We show peptide flip is a common step in the CHAMP/membrane interaction, using other similar CHAMPs: Decoralin, Neurokinin-1, and Temporin-L. Using coarse-grained MD, we studied the CHAMPs peptide concentration effect on vesicles, showing CHAMP-induced membrane budding at highly curved regions of negatively charged vesicles at a high peptide:lipid ratios. Our results suggest that the carpet mode of action fits the description of CHAMPs lysis activity, and we discuss the importance of significant hydrophobic residues in CHAMPs design and activity
- Imprenta:
- Data da defesa: 05.05.2023
- Este periódico é de acesso aberto
- Este artigo é de acesso aberto
- URL de acesso aberto
- Cor do Acesso Aberto: gold
- Licença: cc-by-nc-sa
-
ABNT
PARK, Peter. How do antimicrobial peptides destroy membranes? A Molecular Dynamics perspective. 2023. Tese (Doutorado) – Universidade de São Paulo, São Paulo, 2023. Disponível em: https://www.teses.usp.br/teses/disponiveis/46/46131/tde-11122023-182928/. Acesso em: 03 jun. 2024. -
APA
Park, P. (2023). How do antimicrobial peptides destroy membranes? A Molecular Dynamics perspective (Tese (Doutorado). Universidade de São Paulo, São Paulo. Recuperado de https://www.teses.usp.br/teses/disponiveis/46/46131/tde-11122023-182928/ -
NLM
Park P. How do antimicrobial peptides destroy membranes? A Molecular Dynamics perspective [Internet]. 2023 ;[citado 2024 jun. 03 ] Available from: https://www.teses.usp.br/teses/disponiveis/46/46131/tde-11122023-182928/ -
Vancouver
Park P. How do antimicrobial peptides destroy membranes? A Molecular Dynamics perspective [Internet]. 2023 ;[citado 2024 jun. 03 ] Available from: https://www.teses.usp.br/teses/disponiveis/46/46131/tde-11122023-182928/ - The antimicrobial peptide BP100 induces protrusions in planar membranes and vesicles
- Desenvolvimento computacional de proteínas bloqueadoras da entrada viral do SARS-CoV-2 para o tratamento da COVID-19
- Análise da estrutura secundária do peptídeo analgésico inovador TAT-QYP usando simulações de Dinâmica Molecular
- Vesicle protrusion induced by antimicrobial peptides suggests common carpet mechanism for short antimicrobial peptides
- Simulations reveal that antimicrobial BP100 induces local membrane thinning, slows lipid dynamics and favors water penetration
- Position matters in ester thiolysis by cysteine-containing peptides in micelles and vesicles
Informações sobre o DOI: 10.11606/T.46.2023.tde-11122023-182928 (Fonte: oaDOI API)
How to cite
A citação é gerada automaticamente e pode não estar totalmente de acordo com as normas
