Molecular dynamics simulation of short peptide in DPC micelle using explicit water solvent parameters

Abstract

Short antimicrobial peptide, A4W, have been studied by molecular dynamics (MD) simulation in an explicit dodecylphosphocholine (DPC) micelle. Peptide was aligned with DPC micelle and transferred new peptide-micelle coordinates within the same solvent box using specific micelle topology parameters. After initial energy minimization and equilibration, the conformation and orientation of the peptide were analyzed from trajectories obtained from the RMD (restrained molecular dynamics) or the subsequent free MD. Also, the information of solvation in the backbone and the side chain of the peptide, hydrogen bonding, and the properties of the dynamics were obtained. The results showed that the backbone residues of peptide are either solvated using water or in other case, they relate to hydrogen bonding. These properties could be a critical factor against the insertion mode of interaction. Most of the peptide-micelle interactions come from the hydrophobic interaction between the side chains of peptide and the structural interior of micelle system. The interaction of peptide-micelle, electrostatic potential and hydrogen bonding, between the terminal residues of peptide and the headgroups in micelle were observed. These interactions could be effect on the structure and flexibility of the peptide terminus.

Figure 1. Energy minimized models of DPC micelles (left) and A4W peptide (right). The whole systems were minimized in TIP3P explicit water molecules using AMBER9. The water molecules were represented as triangle with red (oxygen) and white (hydrogen) color, respectively. Hydrophilic headgroups and hydrophobic tails were shown by blue ball and green stick, respectively.

Figure 2. Snapshots at different times along the simulation of a system composed of DPC lipids, water molecules, and A4W peptide. Colors and representations are the same as Figure 1. The position of the peptide and lipids at initial stage (0 ps, left) and one of the positions of the peptide after a 20 ps simulation (right) were shown, respectively.

Figure 3. RMS difference for A4W-solvent-micelle system during molecular dynamics simulation. The least square fit of position of C-alpha was calculated in model after MD (left), and RMS fluctuation of A4W in solvent-micelle system was calculated in fs scale (right).

Figure 4. Total GROMACS energies (left) and partial densities (right) of A4W-solvent-micelle system were represented in ps time scale and in nm periodic box scale.

Table 1. Molecular systems used for molecular dynamics simulations.