Molecular dynamics trajectories for the aggregation of IAPP₁₁₋₂₉ with chondroitin-4-sulfate and POPC bilayers

About this repository This repository contains coarse-grained molecular dynamics trajectories from a study of how the human islet amyloid polypeptide fragment IAPP₁₁₋₂₉ aggregates in the presence of chondroitin-4-sulfate (CS, a glycosaminoglycan), POPC lipid bilayers, or both. The simulations probe three assembly pathways, designed to disentangle the independent, simultaneous, and sequential contributions of CS and zwitterionic lipid bilayers to amyloid peptide aggregation. The three assembly pathways are: A1: 13 IAPP(11-29) monomers, one dp44 CS chain, and a pre-equilibrated POPC bilayer are combined simultaneously in solvent. Peptides and CS are placed above the bilayer's upper leaflet.A2: A pre-formed IAPP–CS complex (taken from t = 750 ns of the IAPP+CS reference simulation) is placed in the solvent slab of a pre-equilibrated POPC bilayer. A3_FDS: A CS chain is introduced to a configuration in which IAPP peptides are fully adsorbed on the POPC bilayer as dispersed small oligomers (FDS state). The starting coordinates are taken from t = 750 ns of a IAPP+PC reference simulation that reached this state. The CS+ (CS introduced) and CS− (continued without CS) are subfolders for simulations with and without CS. A3_PCL: A CS chain is introduced to a configuration in which IAPP peptides have formed a single large aggregate only partially in contact with the bilayer (PCL state). The starting coordinates are taken from t = 750 ns of a IAPP+PC reference simulation that reached this state. The CS+ (CS introduced) and CS− (continued without CS) are subfolders for simulations with and without CS. Two-component reference simulations are: IAPP_CS: 13 IAPP(11-29) monomers are introduced with a dp44 CS chain in aqueous solvent (no bilayer) IAPP_PC: 13 IAPP(11-29) monomers are introduced near a POPC lipid bilayer (no CS) All simulations were performed with GROMACS 2019.4, using the ProMPT force field for IAPP(11-29), the WEPMEM force field forReproducing the simulations POPC, a new CG chondroitin-4-sulfate parameter set introduced in the associated publication, and the MARTINI polarizable water model with monovalent ions at 150 mM. Three independent replicas of 1500 ns each were performed per system with unique starting velocities, unless otherwise noted under Notes on specific systems below. Contents The repository contains the file iapp_cs_pc_trajectories.zip, with the following structure: iapp_cs_pc_trajectories/ ├── A1_simultaneous/ │ ├── solute_only.ndx │ ├── trial1/ │ ├── trial2/ │ └── trial3/ ├── A2_preformed_complex/ │ ├── solute_only.ndx │ ├── trial1/ │ └── trial2/ ├── A3_FDS/ │ ├── CS+/ │ │ ├── solute_only.ndx │ │ ├── trial1/ │ │ ├── trial2/ │ │ └── trial3/ │ └── CS-/ │ ├── solute_only.ndx │ ├── trial1/ │ ├── trial2/ │ └── trial3/ ├── A3_PCL/ │ ├── CS+/ │ │ ├── solute_only.ndx │ │ ├── trial1/ │ │ ├── trial2/ │ │ └── trial3/ │ └── CS-/ │ ├── solute_only.ndx │ ├── trial1/ │ ├── trial2/ │ └── trial3/ └── reference_simulations/ ├── IAPP_CS/ │ ├── solute_only.ndx │ ├── trial1/ │ ├── trial2/ │ └── trial3/ └── IAPP_PC/ ├── solute_only.ndx ├── trial1/ ├── trial2/ ├── trial3/ ├── trial4/ ├── trial5/ └── trial6/ Each trial folder contains: md.tpr — Portable run file for the full simulated system. May be used to reproduce or extend the trajectory. traj.solute_only.xtc — Production trajectory with MARTINI polarizable water removed, centered with gmx trjconv. Peptides, CS, POPC lipids, and ions are retained where present. md.solute_only.tpr — Portable binary input file matching traj.solute_only.xtc, generated with gmx convert-tpr. Use for analysis of the water-stripped trajectory. solute_only.psf — Protein structure file for VMD visualization of traj.solute_only.xtc. Each system folder also contains solute_only.ndx, the index file defining the atom groups used to generate the water-stripped files. Reproducing the simulations For force field parameter files, .mdp settings, INSANE inputs for bilayer generation, and a tutorial on setting up new systems, see the companion GitHub repository: [GitHub URL] Visualization To visualize a trajectory in VMD, load the solute_only.psf first, then load traj.solute_only.xtc into the same molecule.