Computing structure-based lipid accessibility of membrane proteins with mp_lipid_acc in RosettaMP
By Julia Koehler Leman, Sergey Lyskov, Richard Bonneau. 2016
27 citations recorded by the source corpus.
Membrane proteins are underrepresented in structural databases, which has led to a lack of computational tools and the corresponding inappropriate use of tools designed for soluble proteins. For membrane proteins, lipid accessibility is an essential property. Although programs are available for sequence-based prediction of lipid accessibility and structure-based identification of solvent-accessible surface area, the latter does not distinguish between water accessible and lipid accessible residues in membrane proteins. Here we present mp_lipid_acc, the first method to identify lipid accessible residues from the protein structure, implemented in the RosettaMP framework and available as a webserver. Our method uses protein structures transformed in membrane coordinates, for instance from PDBTM or OPM databases, and a defined membrane thickness to classify lipid accessibility of residues. mp_lipid_acc is applicable to both α-helical and β-barrel membrane proteins of diverse architectures with or without water-filled pores and uses a concave hull algorithm for surface-residue classification. We further provide a manually curated benchmark dataset that can be used for further method development. We present a novel tool to classify lipid accessibility from the protein structure, which is applicable to proteins of diverse architectures and achieves prediction accuracies of 90% on a manually curated database. mp_lipid_acc is part of the Rosetta software suite, available at www.rosettacommons.org. The webserver is available at http://rosie.graylab.jhu.edu/mp_lipid_acc/submit and the benchmark dataset is available at http://tinyurl.com/mp-lipid-acc-dataset.
Subfields: Molecular Biology
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In Molecular Biology
- Jeffrey J. Gray
- Jens Meiler
- Xingjie Pan
- Tanja Kortemme
- Sergey Lyskov
- Rhiju Das
- David Baker
- Rebecca F. Alford
Citations in the corpus
- Recent advances in de novo protein design: Principles, methods, and applications (2021, methodology): “The interface between bulk water and bulk lipid is modeled as a continuous transition of hydration fraction, with water-filled pores modeled using a convex-hull algorithm (125).”
- Protein Structure Prediction and Design in a Biologically Realistic Implicit Membrane. (2020, background): “(43) and was chosen because it is the largest possible subset of high-resolution structures with diverse sequences, further filtered for proteins with known host lipid compositions.”
- Web‐accessible molecular modeling with Rosetta: The Rosetta Online Server that Includes Everyone (ROSIE) (2018, background): “60 This annotated PDB can then be viewed in standard molecular viewers.”