Tilted State Population of Antimicrobial Peptide PGLa Is Coupled to the Transmembrane Potential

Cationic antimicrobial peptide PGLa gets into close contact
with
the anionic bacterial cell membrane, facilitating cross-membrane transport
phenomena and membrane disruption depending on the concentration.
The mechanisms of action are closely associated with the tilted insertion
geometry of PGLa. Therefore, we aimed to understand the interaction
between the transmembrane potential (TMP) and the orientation of the
membrane-bound PGLa helix. Molecular dynamics simulations were performed
with TMP, and we found that the PGLa tilt angle relative to the membrane
is coupled with the TMP. Elevated TMP increases the population of
the tilted state. We observed positive feedback between the tilt angle
and the TMP, which occurs due to the electrostatic interaction between
the peptidic helix and the Na+ cations at the membrane–water
interface. These TMP coupled phenomena can contribute to understanding
the direct antimicrobial and adjuvant effects of PGLa in combination
with regular antibiotics.