Aggregation of hydrophobically modified chondroitin sulfate and its interaction with model lipid bilayers - Detailed Simulation Data
Description
This repository contains simulated trajectories of hydrophobically modified chondroitin sulfate (CS). CS, along with hyaluronic acid and chitosan, is a part of a larger group of compounds known as glycosaminoglycans (GAGs) - biopolymers that are commonly found in many organisms. The modification involved attaching hydrophobic 18-carbon long alkyl side plain CS via amide linkages. We set out to investigate, with the aid of molecular dynamics (MD) simulations, the mechanism of CS aggregation at the single-atom scale. Additionally, we were interested in the interactions of these polymers with molecular membranes. The aim was to further the knowledge of using hydrophobically modified glycosaminoglycans (HMGAGs) in applications such as drug delivery systems (DDSs). To this end, five simulation boxes were prepared, each of which consisted of the same POPC membrane (square, 1152 lipids), K+ and Cl- ions (for a total ionic strength of 0.14 mol/dm3), water and an oligomer of hydrophobically modified chondroitin sulfate with a C18 alkyl chain attached to the side (CS-C18). Five DS values were investigated: 0% (A1, for a pure CS), 10% (A2), 25% (A3), 40% (A4), and 100% (A5). One oligomer of each type was placed on the membrane, such that there was no overlap between the oligomer and membrane atoms. Each system has undergone a similar treatment of vacuum minimization, solvent addition, ion addition, minimization, equilibration in an NVT ensemble, equilibration in an NpT ensemble and a 100ns production NpT ensemble simulation. Temperature was kept at 298K by the v-rescale (modified Berendsen) thermostat, while the pressure was kept at 1 bar with a Parinello-Rahman barostat. The results are exciting - displaying that under the examined conditions in 3 out of 4 systems the containing hydrophobically modified oligomers the side chains seem to anchor themselves in the membrane, some at an early stage of the simulation.
Files
Steps to reproduce
The software package used was GROMACS (https://www.gromacs.org/), with the CHARMM36 (https://www.charmm.org/archive/charmm/resources/charmm-force-fields/) forcefield. Part of the configurations was generated using the CHARMM-GUI online system preparation tool, while the remainder of the prep work and analysis was done with in-house software. Visualisations were created using VMD (https://www.ks.uiuc.edu/Research/vmd/) - an open source molecular dynamics visualisation software, the POV-Ray (https://www.povray.org/) raytracing engine to perform the rendering, and FFmpeg (https://ffmpeg.org/) multimedia toolkit to create the final output from POV-ray output images.