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bioRxiv · 10.1101/2020.12.11.404764

The effect of acidic pH on the interaction and lytic activity of MP1 and its H-MP1 analog in anionic lipid membrane: a biophysical study by Molecular Dynamics and Spectroscopy

Bernardes Santana Martins, I.·Giordano Viegas, T.·Suman de Araujo, A.·Ruggiero Neto, J.·Monson de Souza, B.·Palma, M. S.
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Abstract

Antimicrobial peptides (AMPs) are part of the innate immune system of many species and are compounds with potential application against the development of resistant bacterial strains promoted by conventional antibiotics. The AMPs are rich in cationic and hydrophobic residues and act directly on the lipidic phase of the cell membranes. The MP1 has a broad-spectrum bactericide activity in both Gram-negative and positive bacteria, not being hemolytic or cytotoxic. H-MP1 is a synthetic analog of MP1 with lysines replaced by histidines so that its net charge could be responsive to changes in solution pH. In the present work, we investigated the effect of the solution pH on the structural properties, in the adsorption and insertion, and on the lytic activity of these peptides in lipid bilayers mimicking the cell membrane of Gram-negative bacteria, using experimental and computational biophysical techniques. The results indicate that the lytic activity of H-MP1 is sensitive to pH, increasing to an acidic environment, matching that of MP1, which is not influenced by solution pH. Molecular Dynamic simulations indicated that the adsorption process of both peptides started by the interaction of the N-terminus with the bilayer, followed by the complete adsorption of the peptide laying parallel to the bilayer plane, inducing an increase in the peptides helical content enhancing peptides contact with the bilayer hydrophobic phase.

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Bernardes Santana Martins, I., Giordano Viegas, T., Suman de Araujo, A., Ruggiero Neto, J., Monson de Souza, B., Palma, M. S.. 2020-12-11. The effect of acidic pH on the interaction and lytic activity of MP1 and its H-MP1 analog in anionic lipid membrane: a biophysical study by Molecular Dynamics and Spectroscopy. https://doi.org/10.1101/2020.12.11.404764

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