After building the system coordinates for molecular dynamics simulations, create a submission script to minimize and relax the built coordinate system. Use the commands listed until hashtag production comment in the README file provided in the output from CHARMM-GUI to the submission script. Submit the relaxation script and ensure all output files from its steps have been produced before progressing to the production run.
Upon completion, verify the presence of output files with different extensions generated from GROMACS during the six-step relaxation run. To perform benchmarking, generate short trajectories one to two nanoseconds long and estimate the computational cost using varying numbers of computing nodes. Compare the performance in nanoseconds per day for different numbers of computing nodes to determine the optimal resources for the run.
Choose the number of nodes that result in a performance level between 75 to 80%of the maximum. Compress raw trajectory files denoted as trr files in GROMACS by changing the file format to xtc files or skipping frames to reduce file size to facilitate efficient transfer to the local station for visualization and analysis. Visualize the full trajectory before running any analysis to identify the molecules or atoms of interest and determine the trajectory portion intended for characterization.
Then determine the area per lipid time series for membrane only simulations and identify the portion of the trajectory. Analysis of membrane structure revealed a significant difference in thickness between the two models for the endoplasmic reticulum, indicating an inverse relationship between the area per lipid and membrane thickness. Deuterium order parameters of each lipid species showed that there is little to no difference between the order of lipid tails between the models except for DPPE, which shows a slight increase for the SN1 tail in the PI model.
Lipid composition and membrane models modulates interactions with other molecules. For example, simulations using different ratios of PC and PS lipids showed that electrostatic interactions drive the initial binding of D112, a delocalized lipophilic cation to anionic lipids and hydrophobic interactions pull the molecule into the membrane core.
