The effect of structural parameters and positive charge distance on the interaction free energy of antimicrobial peptides with membrane surface

Abstract

Many attempts have been made to find hints explaining the relationship between physicochemical and structural properties of antimicrobial peptides (AMPs) which are relevant to their antimicrobial activities. We here found that there is a difference in the percentages of hydrophobic, hydrophilic, and charged residues between AMPs killing both bacteria and fungi (Group A) and AMPs that only kill bacteria (Group B). The percentage of charged residues in Group A AMPs is highly elevated, while in Group B the percentage of hydrophobic residues is increased. This result suggests a sequence-based mechanism of selectivity for AMPs. Moreover, we examined how the distance between basic residues affects the interaction free energy of AMPs with the membrane surface, since most of the known AMPs act by membrane perturbation. We measured the average distance between basic residues throughout the 3D structure of AMPs by defining D_pr parameter and calculated the interaction free energy for 10 AMPs that interacted with the DPPC membrane using molecular dynamics simulation. We found that the changes of the interaction free energy correlates with the change of D_pr by a linear regression coefficient of r²= .47 and a cubic regression coefficient of r²= .70.

Keywords:

• antimicrobial peptides
• charge distribution
• free energy
• molecular dynamics simulation
• drug design

Acknowledgements

We gratefully acknowledge to Ghazaleh Ghavami for her help in running of simulations.