Abstract
Antimicrobial peptides (AMPs) play important roles in the innate immune system of many organisms. Although AMPs have been essentially studied and received increasing attention as potential alternatives against infectious diseases, their use as anticancer peptides (ACPs) in cancer therapy either alone or in combination with other conventional drugs has been considered to be a therapeutic strategy to explore. Recently, We have developed a MD-POPC simulation model to examine the relationship of inserting depth as well as energy statistical calculation between membranes and peptides corresponding to the NMR results. Furthermore, we also proposed a SMD-POPC/POPG simulation model to perform with antimicrobial peptide, WLK and its’ isomers, which design is dependent on the characteristics of helicity and amphipathicity. In bioactivity experiment experiments, the assays of the WLK analogues were showed that WLK11 possess strong antimicrobial, anticancer and low hemolytic activity. Additionally, the biophysical experiments, including circular dichroism and two-dimensional NMR, were used to demonstrate that the stronger antibacterial and salt resistance of WLK11 could be due to the membrane immersion depth. The results of MD simulations demonstrate that the MD statistical calculations of non-bonded energy are positively correlated to the MIC value and cancer cytotoxicity. The assay of antimicrobial and anticancer ability can verify our SMD simulation systems and provide us the in-depth view between the activity and several biophysical properties. To sum up, our work opens a new avenue to develop a potent tool to help us predict not only novel potential AMPs but promising ACPs.