Study of the antimicrobial peptide indolicidin and mutants in eukaryotic modelled membrane by molecular dynamics simulations

Abstract

In this work the interaction of the antimicrobial peptide indolicidin (IND) and its mutants CP10A and CP11 with a eukaryotic membrane model was examined by molecular dynamics simulations. The aim was to analyse the behaviour of these antimicrobial peptides when they interact with a eukaryotic modelled membrane, thereby obtaining atomic detailed observations that are not experimentally available. In the simulations, the widely studied dipalmitoylphosphatidylcholine hydrated bilayer was used as a eukaryotic membrane model. In agreement with experimental observations, the peptides IND, CP10A, and CP11 insert into the bilayer differently; the peptides that insert more deeply present the major hemolytic activities. The hydrophobic residues are responsible for the insertion, but some Trp residues of the peptides remain at the bilayer/water interface because they interact with the bilayer choline groups by cation-π interactions that should be important for recognition of eukaryotic membrane by the three studied peptides.

Keywords:

• antimicrobial peptide indolicidin
• peptide-membrane interaction
• cation-π interaction
• molecular dynamics simulation

Acknowledgements

The authors thank the Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for financial support.