Abstract: A lot of experimental studies indicated that the antimicrobial activity of LL-37 is closely related to the content of helix and the pH value had heavy impact on the formation of secondary helical structure. Here we focused on the pH-dependent conformational characteristics of LL-37 with molecular dynamics simulations. All simulations were performed with the GROMACS software package, OPLS-AA/L force field, periodic boundary conditions, at constant temperature (300 K) and pressure (1 bar). Two independent simulations were performed under neutral (pH=7) and strongly alkaline (pH=12) aqueous solution, respectively. The pH=7.0 and pH=12.0 environment were simulated with all lysine and arginine residues side chain protonated or deprotonated, respectively. Each simulation lasted for 500ns.
The results indicate that the helical content of LL-37 increased with the increasing of solution pH value. The root mean square deviation of residues was smaller at neutral pH than that at high pH, which meant that the conformation of LL-37 became more stable at high pH solution. For the core region of antimicrobial activity (residues 18-29), there were more residues forming -helical structures at high pH than those at neutral pH. Interestingly, LL-37 is an intrinsically disorder protein, but its core region of antimicrobial activity is assigned as ordered by software SPINE-D. The further study of this region may be helpful to understanding its mechanism of broad spectrum of antimicrobial activities and the characteristics of intrinsically disordered proteins.
Acknowledgement: This work was supported by grant 61271378 from the National Natural Science Foundation of China