LiPyphilic: A Python toolkit for the analysis of lipid membrane simulations

Smith, Paul; Lorenz, Christian D.

doi:10.1101/2021.05.04.442445

Cited by 10 publications

(9 citation statements)

References 65 publications

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“…There have also been several recent packages developed which are aimed at analysis of lipid bilayers. These include, e.g., LiPyphilic, 68 which is a fast Python package for analyzing complex lipid bilayer simulations (but not yet extended to membrane proteins), and FATSLiM, 69 also in Python, which enables bilayer leaflet identification and bilayer thickness and area per lipid calculations, and which works for various (curved) membrane geometries and bilayers including proteins. In terms of more detailed analysis of interactions at binding sites, there are several more general approaches for drug-target residence times via simulations, including, e.g., τRAMD, 70 which may in principle be adaptable to protein− lipid interactions.…”

Section: ■ Discussion and Conclusionmentioning

confidence: 99%

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

Song

Corey

Ansell

et al. 2022

J. Chem. Theory Comput.

114

123

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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.

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Section: ■ Discussion and Conclusionmentioning

confidence: 99%

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

Song

Corey

Ansell

et al. 2022

J. Chem. Theory Comput.

114

123

View full text Add to dashboard Cite

show abstract

“…These might not necessarily be optimal for looking at specific protein-lipid interactions but might offer useful tools for looking at the interaction of the PMP with the membrane more generally, including how the membrane changes upon PMP binding. Of particular note are FATSLiM (116), MemSurfer (117), LOOS (118,119) and LiPyphilic (120). This range of programs, along with ProLint and PyLipID mentioned above, showcase the increasing desire for more rigorous and detailed analyses of membrane simulations, and the impressive commitment of the academic community to fulfil this demand.…”

Section: Dedicated Analytical Tools For Analysis and Identification O...mentioning

confidence: 99%

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

et al. 2022

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Peripheral membrane proteins can reversibly and specifically bind to biological membranes to carry out functions such as cell signalling, enzymatic activity, or membrane remodelling. Structures of these proteins and of their lipid-binding domains are typically solved in a soluble form, sometimes with a lipid or lipid headgroup at the binding site. To provide a detailed molecular view of peripheral membrane protein interactions with the membrane, computational methods such as molecular dynamics (MD) simulations can be applied. Here, we outline recent attempts to characterise these binding interactions, focusing on both intracellular proteins, such as PIP-binding domains, and extracellular proteins such as glycolipid-binding bacterial exotoxins. We compare methods used to identify and analyse lipid binding sites from simulation data and highlight recent work characterising the energetics of these interactions using free energy calculations. We describe how improvements in methodologies and computing power will help MD simulations to continue to contribute to this field in the future.

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“…Lipid acyl chain order was characterized by the average deuterium order parameter of all carbons in a lipid's tails, S CC , as used to quantify membrane order in Seo et al [81]. S CC was calculated using LiPyphilic [82].…”

Section: Lipid Acyl Chain Order Parametermentioning

confidence: 99%

Ceramide-1-phosphate transfer protein enhances lipid transport by disrupting hydrophobic lipid–membrane contacts

Rogers

Geissler

2022

Preprint

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Cellular distributions of the sphingolipid ceramide-1-phosphate (C1P) impact essential biological processes. C1P levels are spatiotemporally regulated by ceramide-1-phosphate transfer protein (CPTP), which efficiently shuttles C1P between organelle membranes. Yet, how CPTP rapidly extracts and inserts C1P into a membrane remains unknown. Here, we devise a multiscale simulation approach to elucidate the biophysical details of CPTP-mediated C1P transport. We find that CPTP binds a membrane poised to extract and insert C1P and that membrane binding promotes conformational changes in CPTP that facilitate C1P uptake and release. By substantially disrupting a lipid's local hydrophobic environment in the membrane, CPTP lowers the activation free energy barrier for passive C1P desorption and enhances C1P extraction from the membrane. Upon uptake of C1P, further conformational changes may aid membrane unbinding in a manner reminiscent of the electrostatic switching mechanism used by other lipid transfer proteins. Most notably, we provide molecular evidence for CPTP's ability to catalyze C1P transport by breaking hydrophobic C1P–membrane contacts. Since this catalytic mechanism is biophysically related to that of passive lipid transport, it may be ubiquitously used by lipid transport proteins to rapidly traffic lipids between membranes and ensure membrane homeostasis.

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LiPyphilic: A Python toolkit for the analysis of lipid membrane simulations

Cited by 10 publications

References 65 publications

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

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

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

Ceramide-1-phosphate transfer protein enhances lipid transport by disrupting hydrophobic lipid–membrane contacts

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