Prediction of amphipathic helix-membrane interactions with Rosetta.

Amphipathic helices have hydrophobic and hydrophilic/charged residues situated on opposite faces of the helix. They can anchor peripheral membrane proteins to the membrane, be attached to integral membrane proteins, or exist as independent peptides. Despite the widespread presence of membrane-intera...

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Main Authors: Alican Gulsevin, Jens Meiler
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-03-01
Series:PLoS Computational Biology
Online Access:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008818&type=printable
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author Alican Gulsevin
Jens Meiler
author_facet Alican Gulsevin
Jens Meiler
author_sort Alican Gulsevin
collection DOAJ
description Amphipathic helices have hydrophobic and hydrophilic/charged residues situated on opposite faces of the helix. They can anchor peripheral membrane proteins to the membrane, be attached to integral membrane proteins, or exist as independent peptides. Despite the widespread presence of membrane-interacting amphipathic helices, there is no computational tool within Rosetta to model their interactions with membranes. In order to address this need, we developed the AmphiScan protocol with PyRosetta, which runs a grid search to find the most favorable position of an amphipathic helix with respect to the membrane. The performance of the algorithm was tested in benchmarks with the RosettaMembrane, ref2015_memb, and franklin2019 score functions on six engineered and 44 naturally-occurring amphipathic helices using membrane coordinates from the OPM and PDBTM databases, OREMPRO server, and MD simulations for comparison. The AmphiScan protocol predicted the coordinates of amphipathic helices within less than 3Å of the reference structures and identified membrane-embedded residues with a Matthews Correlation Constant (MCC) of up to 0.57. Overall, AmphiScan stands as fast, accurate, and highly-customizable protocol that can be pipelined with other Rosetta and Python applications.
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spelling doaj-art-465934a3d0804820a4401e4346c360bc2025-08-20T02:18:00ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-03-01173e100881810.1371/journal.pcbi.1008818Prediction of amphipathic helix-membrane interactions with Rosetta.Alican GulsevinJens MeilerAmphipathic helices have hydrophobic and hydrophilic/charged residues situated on opposite faces of the helix. They can anchor peripheral membrane proteins to the membrane, be attached to integral membrane proteins, or exist as independent peptides. Despite the widespread presence of membrane-interacting amphipathic helices, there is no computational tool within Rosetta to model their interactions with membranes. In order to address this need, we developed the AmphiScan protocol with PyRosetta, which runs a grid search to find the most favorable position of an amphipathic helix with respect to the membrane. The performance of the algorithm was tested in benchmarks with the RosettaMembrane, ref2015_memb, and franklin2019 score functions on six engineered and 44 naturally-occurring amphipathic helices using membrane coordinates from the OPM and PDBTM databases, OREMPRO server, and MD simulations for comparison. The AmphiScan protocol predicted the coordinates of amphipathic helices within less than 3Å of the reference structures and identified membrane-embedded residues with a Matthews Correlation Constant (MCC) of up to 0.57. Overall, AmphiScan stands as fast, accurate, and highly-customizable protocol that can be pipelined with other Rosetta and Python applications.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008818&type=printable
spellingShingle Alican Gulsevin
Jens Meiler
Prediction of amphipathic helix-membrane interactions with Rosetta.
PLoS Computational Biology
title Prediction of amphipathic helix-membrane interactions with Rosetta.
title_full Prediction of amphipathic helix-membrane interactions with Rosetta.
title_fullStr Prediction of amphipathic helix-membrane interactions with Rosetta.
title_full_unstemmed Prediction of amphipathic helix-membrane interactions with Rosetta.
title_short Prediction of amphipathic helix-membrane interactions with Rosetta.
title_sort prediction of amphipathic helix membrane interactions with rosetta
url https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008818&type=printable
work_keys_str_mv AT alicangulsevin predictionofamphipathichelixmembraneinteractionswithrosetta
AT jensmeiler predictionofamphipathichelixmembraneinteractionswithrosetta