The potential of antimicrobial peptides (AMPs) as an alternative to conventional therapies is well recognized. Insights into the biological and biophysical properties of AMPs are thus key to understanding their mode of action. In this study, the mechanisms adopted by two AMPs in disrupting the gram-negative Escherichia coli bacterial envelope were explored. BP100 is a short cecropin A-melittin hybrid peptide known to inhibit the growth of phytopathogenic gram-negative bacteria. pepR, on the other hand, is a novel AMP derived from the dengue virus capsid protein. Both BP100 and pepR were found to inhibit the growth of E. coli at micromolar concentrations. Zeta potential measurements of E. coli incubated with increasing peptide concentrations allowed for the establishment of a correlation between the minimal inhibitory concentration (MIC) of each AMP and membrane surface charge neutralization. While a neutralization-mediated killing mechanism adopted by either AMP is not necessarily implied, the hypothesis that surface neutralization occurs close to MIC values was confirmed. Atomic force microscopy (AFM) was then employed to visualize the structural effect of the interaction of each AMP with the E. coli cell envelope. At their MICs, BP100 and pepR progressively destroyed the bacterial envelope, with extensive damage already occurring 2 h after peptide addition to the bacteria. A similar effect was observed for each AMP in the concentration-dependent studies. At peptide concentrations below MIC values, only minor disruptions of the bacterial surface occurred.

Hydrodynamic properties (translational diffusion, sedimentation coefficients and correlation times) of short B-DNA oligonucleotides are calculated from the atomic-level structure using a bead modeling procedure in which each non-hydrogen atom is represented by a bead. Using available experimental data of hydrodynamic properties for several oligonucleotides, the best fit for the hydrodynamic radius of the atoms is found to be ∼2.8 Å. Using this value, the predictions for the properties corresponding to translational motion and end-over-end rotation are accurate to within a few percent error. Analysis of NMR correlation times requires accounting for the internal flexibility of the double helix, and allows an estimation of ∼0.85 for the Lipari–Szabo generalized order parameter. Also, the degree of hydration can be determined from hydrodynamics, with a result of ∼0.3 g (water)/g (DNA). These numerical results are quite similar to those found for globular proteins. If the hydrodynamic model for the short DNA is simply a cylindrical rod, the predictions for overall translation and rotation are slightly worse, but the NMR correlation times and the degree of hydration, which depend more on the cross-sectional structure, are more severely affected.