Molecular dynamics simulation data of ELIC in nanodiscs

Arcario, Mark1

Published Dec 08, 2023 on Dryad. https://doi.org/10.5061/dryad.z8w9ghxk5

Data files

Dec 08, 2023 version files 81.23 GB

11nm_nanodisc.zip

38.07 GB
9nm_nanodisc.zip

30.06 GB
bilayer.zip

13.10 GB
propylamine.str

2.33 KB
README.md

3.11 KB
scripts.zip

15.32 KB

Abstract

Lipid nanodiscs have become a standard tool for studying membrane proteins, including using single particle cryo-electron microscopy (cryo-EM). We find that reconstituting the pentameric ligand-gated ion channel (pLGIC), Erwinia ligand-gated ion channel (ELIC), in different nanodiscs produces distinct structures by cryo-EM. The effect of the nanodisc on ELIC structure extends to the extracellular domain and agonist binding site. Additionally, molecular dynamic simulations indicate that nanodiscs of different sizes impact ELIC structure and that the nanodisc scaffold directly interacts with ELIC. These findings suggest that the nanodisc plays a crucial role in determining the structure of pLGICs, and that reconstitution of ion channels in larger nanodiscs may better approximate a lipid membrane environment.

README: Molecular Dynamics Simulation Data of ELIC in Nanodiscs

https://doi.org/10.5061/dryad.z8w9ghxk5

This data set is associated with Nature Communications (Manuscript Control Number: NCOMMS-22-45947). Contained here are three sets of molecular dynamics (MD) simulation trajectories described in the manuscript: ELIC wild-type in POPC planar bilayer, ELIC wild-type in a 9 nm nanodisc containing POPC, and ELIC wild-type in an 11 nm nanodisc containing POPC. In each simulation condition, three independent replicates were performed. The initial structures were generated with CHARMM-GUI. The MD data was generated using NAMD 2.14. Additional parameters for propylamine were generated with the CGenFF server and are provided here as well.

Description of the data and file structure

At the top level, each simulation condition (i.e., planar bilayer, 9 nm nanodisc, and 11 nm nanodisc) have their own folder. Within each simulation condition, you will find each replicate has its own folder labeled as "Run N" where 'N' is the independent replicate number. Each run directory contains the starting structures (as a '.psf'/'.pdb' pair), configuration files ('.conf'), and a downsampled trajectory file ('.dcd'). In each run directory, you will also find a file labeled 'extraBonds.txt'. This is a NAMD extra bonds file to ensure that the included agonist, propylamine, remained in the binding pocket for the duration of the simulation.

For completeness, the topology and parameter files for propylamine generated by the CGenFF server are also included as a top level file labeled "propylamine.str". These are provided as combined "stream" files (containing both the topology and parameters in a single file. Besides these parameters, the standard CHARMM36 force field parameters were used and are not included here.

Lastly, there is a top level file labeled "scripts". This folder contains the scripts used for data analysis of the included trajectories. There are Tcl and Python scripts. The versions contained herein will not be updated and were the exact scripts used to analyze the data contained herein. See below for a link to a maintained version of these analysis scripts as well as a description of the scripts included.

Sharing/Access information

As stated above, the analysis scripts here will not be updated. There will be a maintained version of the analysis scripts at: https://github.com/mjarcario/NanodiscAnalysis

Code/Software

Within the "Scripts" directory, there are files used for analysis of the trajectory data. "NanodiscAnalysis.tcl" is the main analysis script used for this dataset. It relies on two outside scripts, namely "procedures.tcl" which contains some basic functions and "ellipse.py" which calculates the ellipse of best fit to measure nanodisc diameter. All functions within "nanodiscAnalysis.tcl" are documented as to what the input variables represent and the expected output. This information will not be repeated here. The analysis was performed using VMD (version 1.9.4a55) containing Tcl (version 8.5.6). The Python code was executed using version 3.6.8.