PyLipID: A Python Package for Analysis of Protein–Lipid Interactions from Molecular Dynamics Simulations

Abstract

Lipids play important modulatory and structural roles for membrane proteins. Molecular dynamics simulations are frequently used to provide insights into the nature of these protein−lipid interactions. Systematic comparative analysis requires tools that provide algorithms for objective assessment of such interactions. We introduce PyLipID, a Python package for the identification and characterization of specific lipid interactions and binding sites on membrane proteins from molecular dynamics simulations. PyLipID uses a community analysis approach for binding site detection, calculating lipid residence times for both the individual protein residues and the detected binding sites. To assist structural analysis, PyLipID produces representative bound lipid poses from simulation data, using a density-based scoring function. To estimate residue contacts robustly, PyLipID uses a dual-cutoff scheme to differentiate between lipid conformational rearrangements while bound from full dissociation events. In addition to the characterization of protein−lipid interactions, PyLipID is applicable to analysis of the interactions of membrane proteins with other ligands. By combining automated analysis, efficient algorithms, and open-source distribution, PyLipID facilitates the systematic analysis of lipid interactions from large simulation data sets of multiple species of membrane proteins.

Specific interactions of peripheral membrane proteins with lipids: what can molecular simulations show us?

“…The second tool is PyLipID (113) PyLipID is a Python-based package which reads in trajectory files and creates an interaction profile for each individual residue-lipid pair over the course of the simulation. It then applies a network analysis method to cluster residues which simultaneously binding the same lipid, to allow identification of specific lipid sites.…”

“…The second tool is PyLipID [ 108 ]. PyLipID is a Python-based package which reads in trajectory files and creates an interaction profile for each individual residue–lipid pair over the course of the simulation.…”

Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients

“…To better understand the molecular nature of the interaction between MraY and its membrane-embedded substrates, we carried out extensive MD simulations of the MraY dimer (PDB ID: 5CKR) in a model lipid bilayer containing C 55 -P, lipid I or both (see Methods). We analysed the interactions of MraY with C 55 -P using a graph theory-based network modelling approach ( https://github.com/wlsong/PyLipID ) 28 . The data reveal the presence of several binding sites for C 55 -P and lipid I around the MraY dimer which are occupied for at least 50% of the simulation time.…”

“…Identification of lipid-binding sites was performed following a kinetic analysis of the protein–lipid interactions 49 with a programme freely available at https://github.com/wlsong/PyLipID 28 . A double cut-off of 0.55 and 0.8 nm was used.…”

Subtype-specific responses of hKv7.4 and hKv7.5 channels to polyunsaturated fatty acids reveal an unconventional modulatory site and mechanism

“…Simulations were performed using GROMACS version 2020.4 ( Abraham et al, 2015 ). The analysis of the coarse-grained simulations was carried out using PyLipid ( Song et al, 2022 ). Frames extracted every 20 ns were used for the analysis.…”