LipIDens - simulation assisted interpretation of lipid densities

LipIDens is a pipeline for simulation assisted interpretation of lipid or lipid-like densities in e.g. cryogenic electron microscopy (cryo-EM) structures of membrane proteins. The protocol can be used to establish CG simulations, analyse lipid binding sites using PyLipID, screen, rank and process PyLipID outputs and establish atomistic simulations to refine lipid binding poses.

LipIDens aims to guide the user from 'lipid-like' to 'lipid-site' to assist membrane protein structure interpretation.

Applications:

• Differentiating between sterol and phospholipid binding sites where structural densities are ambiguous.
• Assess preferential binding of different lipid types to a site where lipid-like density is observed.
• Evaluate whether lipid tail densities are likely to belong to the same or adjacent binding sites.
• Quantify the kinetics of different lipids binding to the same site.
• Obtain a more complete picture of lipid interactions profiles around the protein in a membrane environment.
• Assist interpretation of cryo-EM densities during model building and map refinement cycles.
• Assess which putative lipid binding sites may prevail when not in detergent conditions.

Installation:

LipIDens requires a python3 environment (>=3.9 recommended).

LipIDens installation from the GitHub repository:

git clone https://github.com/TBGAnsell/LipIDens
cd LipIDens
python setup.py install

Recomended

Recommended to use dssp version 3 as this is the only current version compatible with martinize2. Check your version using mkdssp --version.

conda install -c salilab dssp

Conda (legacy installation):

conda create -n LipIDens python=3.9
pip install -r requirements.txt

Usage:

Detailed steps for the usage and implementation of LidIDens are provided within the accompanying protocols manuscript (see citation below).

LipIDens can be run using the standalone lipidens_master_run.py (user inputs variables to terminal) or master_run.py (define variables within script a priori) scripts.

python lipidens_master_run.py

Select the required protocol stage when prompted.

In addition, a jupyter notebook tutorial is provided to assist implementation (LipIDens.ipynb).

Citation:

Please cite the following if elements of the LipIDens protocol are used:

Ansell, T.B., Song, W., Coupland, C.E., Carrique, L., Corey, R.A., Duncan, A.L., Cassidy, C.K., Geurts, M.M.G., Rasmussen, T., Ward, A.B., Siebold, C., Stansfeld, P., Sansom, M.S.P. (2022). LipIDens: Simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins. bioRxiv, doi: 10.1101/2022.06.30.498233

Accompanying step by step protocol citation:

Ansell, T.B., Song, W., Coupland, C.E., Carrique, L., Corey, R.A., Duncan, A.L., Cassidy, C.K., Geurts, M.M.G., Rasmussen, T., Ward, A.B., Siebold, C., Stansfeld, P., Sansom, M.S.P. (2023). Implementation of the LipIDens pipeline: assisted interpretation of lipid densities in membrane protein structures using simulations. protocols exchange, doi: 10.21203/rs.3.pex-2408/v1

The LipIDens logo was designed by Jessica Ansell.