Dynamics of activation in the voltage-sensing domain of Ci-VSP

This repository contains custom code for analyzing simulations of Ci-VSD for ref. 1.

Data

Example data to run the create Figure 5 of the publication can be obtained as a file data.tar.gz as Source Data with the accompanying publication. The tarball can be unzipped using tar -xzvf data.tar.gzand the files used to generate the appropriate plots (see notebooks).

Environment

Most of the analysis is performed in Jupyter notebooks. Notebooks to produce relevant figures are under the subfolder figures along with a README file that provides further description. The data

The environment to setup the analysis is using Python 3.9.x, and detailed packages used are listed in requirements.txt. The analysis scripts have only been tested in 3.9.x and will not work in earlier versions (due to package dependencies).

Dependencies

The primary dependencies are Jupyter notebooks

• Numerical analysis
  • numpy<1.22
  • scipy
  • scikit-learn>=1.2
  • numba
• Plotting
  • matplotlib
  • seaborn
  • prettypyplot (https://braniii.gitlab.io/prettypyplot/)
• MD analysis
  • MDAnalysis>=2.0 (MDAnalysis)
  • pyemma 2.5 (PyEMMA)
  • mdtraj 1.9 (MDTraj)
• DGA/TPT analysis (from the Dinner group)
  • extq (DGA)
  • ivac (Integrated VAC)

Other useful utility functions and plotting functions are found in python/util.py and python/plotting.py.

DGA calculations

The code to run DGA calculations is provided in the extq package. The package can be installed by cloning the repository git clone https://github.com/chatipat/extq.git and running pip install -e extq.

To reproduce the DGA calculations, run the notebook dga.ipynb in notebooks/figures using the example data provided.

conda

The easiest way to set up is to use requirements.txt and create a new Conda environment.

conda create --file requirements.txt -n civsd

Or one can create a new environment and install packages as necessary:

conda create -n civsd python=3.9

Files

• Generic scripts to perform CV calculations are found in scripts. These include several tcl scripts to use with VMD.
• Reference crystal structures (see ref. 1) and MD-simulation structures (ref. 2) are found in models.
• Scripts and starting files for setting up biased SMD (steered MD) simulations are in biased/smd-prep. These were used to equilibrate new structures for unbiased simulations by pulling the protein forward and backwards.

References

1. Guo, et al. Dynamics of activation in the voltage-sensing domain of Ci-VSP. bioRxiv 2022.
2. Li, et al. Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain. Nat. Struct. Mol. Bio. 2014.
3. Shen, et al. Mechanism of Voltage Gating in the Voltage-Sensing Phosphatase Ci-VSP. PNAS 2022.