# Numerical Simulation of Interaction between Plasma and Azithromycin Based on Molecular Dynamics
## 2 Modeling and Simulation
### Molecular Structure and Modeling of Azithromycin  
Azithromycin is a commonly used macrolide antibiotic which has a molecular formula of C\({}_{38}\)H\({}_{72}\)N\({}_{3}\). As a representative of ester antibiotics, azithromycin is commonly used in aquaculture and animal feeding. The molecular structure is shown in Figure 1. The structure comprises three-ring systems, and the rings are connected by carbon-oxygen bonds (ether bonds). Its molecule has five alcohol groups, three of which can be oxidized into ketones, one ester group, and five ether bonds.  
The overall molecular dynamics simulation process is shown in Figure 2.  
The modeling of the azithromycin molecule was achieved by using _MaterialsStudio17.1_. With the help of this software, the structure of the azithromycin molecule was drawn, and the correct chemical bonds and forcefields were set as well. The molecular structure was then geometrically optimized with the Forcite module to make it more stable with minimum energy. The specific steps of the simulation are as follows: using the geometry optimization task in the Forcite module, the selection of the NVT ensemble (N represents the number of determined particles, V represents the volume, and T represents the temperature) and the initial velocity of the particles is random. The temperature is set to 298 K, the time step is set to 0.1 fs, and the total simulation time is 100 ps. The processed molecules are shown in Figure 3. Next, using the amorphous cell module to encapsulate the azithromycin molecule with the active particle groups, the Compass forcefield is selected, and the size of the reaction box is about 15 A \(\times\) 15 A \(\times\) 15 A. Then, the dynamics task in the Forcite module is used to balance the system energy, and the other settings are the same as above. The purpose is to compensate or remove part of the energy of the system to achieve a stable state with minimum energy.  
Figure 1: Azithromycin molecular structure.  
Figure 2: Molecular dynamics simulation flowchart.  
Then, the ReaxFF reaction potential was used to simulate the reaction between the active-particle groups generated by the plasma and the azithromycin. According to the molecular dynamics principle, the molecular dynamics simulation's step size should not be too large. Otherwise, the energy will change significantly during the reaction, and the system's total energy will not be conserved. Moreover, if the simulation step is set for too long, the changes of the system cannot be reflected; if it is too short, the output results will be redundant. In this section, we used the dynamics task of the gulp module and selected the ReaxFF forcefield. Additionally, the charge of each atom was specified by the chosen electric forcefield. After several pre-simulations, it was found that the reaction was completed at about 80 ps, so the total reaction time was set to 100 ps to ensure the reaction was done. The temperature was set to 298 K, the system was set to the NVT ensemble, the simulation step time was set to 0.1 fs, the number of steps was 1,000,000 steps, and the results were output every 1000 steps. The size of the reaction box is about 15 A \(\times\) 15 A \(\times\) 15 A \(\times\) 15 A. Every simulations was repeated 20 times independently. This paper focuses on the principle and decomposition path of azithromycin decomposition at the microscopic particle level, so to facilitate observation and analysis, only one azithromycin molecule was selected to react with different numbers of active-particle groups.