Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold

Ion channels play key roles in human physiology and are important targets in drug discovery. The atomic-scale structures of ion channels provide invaluable insights into a fundamental understanding of the molecular mechanisms of channel gating and modulation. Recent breakthroughs in deep learning-ba...

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Main Authors: Phuong Tran Nguyen, Brandon John Harris, Diego Lopez Mateos, Adriana Hernández González, Adam Michael Murray, Vladimir Yarov-Yarovoy
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Channels
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Online Access:https://www.tandfonline.com/doi/10.1080/19336950.2024.2325032
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author Phuong Tran Nguyen
Brandon John Harris
Diego Lopez Mateos
Adriana Hernández González
Adam Michael Murray
Vladimir Yarov-Yarovoy
author_facet Phuong Tran Nguyen
Brandon John Harris
Diego Lopez Mateos
Adriana Hernández González
Adam Michael Murray
Vladimir Yarov-Yarovoy
author_sort Phuong Tran Nguyen
collection DOAJ
description Ion channels play key roles in human physiology and are important targets in drug discovery. The atomic-scale structures of ion channels provide invaluable insights into a fundamental understanding of the molecular mechanisms of channel gating and modulation. Recent breakthroughs in deep learning-based computational methods, such as AlphaFold, RoseTTAFold, and ESMFold have transformed research in protein structure prediction and design. We review the application of AlphaFold, RoseTTAFold, and ESMFold to structural modeling of ion channels using representative voltage-gated ion channels, including human voltage-gated sodium (NaV) channel - NaV1.8, human voltage-gated calcium (CaV) channel – CaV1.1, and human voltage-gated potassium (KV) channel – KV1.3. We compared AlphaFold, RoseTTAFold, and ESMFold structural models of NaV1.8, CaV1.1, and KV1.3 with corresponding cryo-EM structures to assess details of their similarities and differences. Our findings shed light on the strengths and limitations of the current state-of-the-art deep learning-based computational methods for modeling ion channel structures, offering valuable insights to guide their future applications for ion channel research.
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spelling doaj-art-beab5ea70fd84c6f9e25b028bb4eafa22024-12-09T07:27:27ZengTaylor & Francis GroupChannels1933-69501933-69692024-12-0118110.1080/19336950.2024.2325032Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFoldPhuong Tran Nguyen0Brandon John Harris1Diego Lopez Mateos2Adriana Hernández González3Adam Michael Murray4Vladimir Yarov-Yarovoy5Department of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA, USADepartment of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA, USADepartment of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA, USADepartment of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA, USAMonterey Peninsula College, Monterey, CA, USADepartment of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA, USAIon channels play key roles in human physiology and are important targets in drug discovery. The atomic-scale structures of ion channels provide invaluable insights into a fundamental understanding of the molecular mechanisms of channel gating and modulation. Recent breakthroughs in deep learning-based computational methods, such as AlphaFold, RoseTTAFold, and ESMFold have transformed research in protein structure prediction and design. We review the application of AlphaFold, RoseTTAFold, and ESMFold to structural modeling of ion channels using representative voltage-gated ion channels, including human voltage-gated sodium (NaV) channel - NaV1.8, human voltage-gated calcium (CaV) channel – CaV1.1, and human voltage-gated potassium (KV) channel – KV1.3. We compared AlphaFold, RoseTTAFold, and ESMFold structural models of NaV1.8, CaV1.1, and KV1.3 with corresponding cryo-EM structures to assess details of their similarities and differences. Our findings shed light on the strengths and limitations of the current state-of-the-art deep learning-based computational methods for modeling ion channel structures, offering valuable insights to guide their future applications for ion channel research.https://www.tandfonline.com/doi/10.1080/19336950.2024.2325032Structural modelingvoltage-gated sodium channelsvoltage-gated calcium channelsvoltage-gated potassium chnanelsAlphaFoldRoseTTAFold
spellingShingle Phuong Tran Nguyen
Brandon John Harris
Diego Lopez Mateos
Adriana Hernández González
Adam Michael Murray
Vladimir Yarov-Yarovoy
Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold
Channels
Structural modeling
voltage-gated sodium channels
voltage-gated calcium channels
voltage-gated potassium chnanels
AlphaFold
RoseTTAFold
title Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold
title_full Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold
title_fullStr Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold
title_full_unstemmed Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold
title_short Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold
title_sort structural modeling of ion channels using alphafold2 rosettafold2 and esmfold
topic Structural modeling
voltage-gated sodium channels
voltage-gated calcium channels
voltage-gated potassium chnanels
AlphaFold
RoseTTAFold
url https://www.tandfonline.com/doi/10.1080/19336950.2024.2325032
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