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RosettaEPR: Rotamer Library for Spin Label Structure and Dynamics

An increasingly used parameter in structural biology is the measurement of distances between spin labels bound to a protein. One limitation to these measurements is the unknown position of the spin label relative to the protein backbone. To overcome this drawback, we introduce a rotamer library of t...

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Autores principales: Alexander, Nathan S., Stein, Richard A., Koteiche, Hanane A., Kaufmann, Kristian W., Mchaourab, Hassane S., Meiler, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764097/
https://www.ncbi.nlm.nih.gov/pubmed/24039810
http://dx.doi.org/10.1371/journal.pone.0072851
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author Alexander, Nathan S.
Stein, Richard A.
Koteiche, Hanane A.
Kaufmann, Kristian W.
Mchaourab, Hassane S.
Meiler, Jens
author_facet Alexander, Nathan S.
Stein, Richard A.
Koteiche, Hanane A.
Kaufmann, Kristian W.
Mchaourab, Hassane S.
Meiler, Jens
author_sort Alexander, Nathan S.
collection PubMed
description An increasingly used parameter in structural biology is the measurement of distances between spin labels bound to a protein. One limitation to these measurements is the unknown position of the spin label relative to the protein backbone. To overcome this drawback, we introduce a rotamer library of the methanethiosulfonate spin label (MTSSL) into the protein modeling program Rosetta. Spin label rotamers were derived from conformations observed in crystal structures of spin labeled T4 lysozyme and previously published molecular dynamics simulations. Rosetta’s ability to accurately recover spin label conformations and EPR measured distance distributions was evaluated against 19 experimentally determined MTSSL labeled structures of T4 lysozyme and the membrane protein LeuT and 73 distance distributions from T4 lysozyme and the membrane protein MsbA. For a site in the core of T4 lysozyme, the correct spin label conformation (Χ(1) and Χ(2)) is recovered in 99.8% of trials. In surface positions 53% of the trajectories agree with crystallized conformations in Χ(1) and Χ(2). This level of recovery is on par with Rosetta performance for the 20 natural amino acids. In addition, Rosetta predicts the distance between two spin labels with a mean error of 4.4 Å. The width of the experimental distance distribution, which reflects the flexibility of the two spin labels, is predicted with a mean error of 1.3 Å. RosettaEPR makes full-atom spin label modeling available to a wide scientific community in conjunction with the powerful suite of modeling methods within Rosetta.
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spelling pubmed-37640972013-09-13 RosettaEPR: Rotamer Library for Spin Label Structure and Dynamics Alexander, Nathan S. Stein, Richard A. Koteiche, Hanane A. Kaufmann, Kristian W. Mchaourab, Hassane S. Meiler, Jens PLoS One Research Article An increasingly used parameter in structural biology is the measurement of distances between spin labels bound to a protein. One limitation to these measurements is the unknown position of the spin label relative to the protein backbone. To overcome this drawback, we introduce a rotamer library of the methanethiosulfonate spin label (MTSSL) into the protein modeling program Rosetta. Spin label rotamers were derived from conformations observed in crystal structures of spin labeled T4 lysozyme and previously published molecular dynamics simulations. Rosetta’s ability to accurately recover spin label conformations and EPR measured distance distributions was evaluated against 19 experimentally determined MTSSL labeled structures of T4 lysozyme and the membrane protein LeuT and 73 distance distributions from T4 lysozyme and the membrane protein MsbA. For a site in the core of T4 lysozyme, the correct spin label conformation (Χ(1) and Χ(2)) is recovered in 99.8% of trials. In surface positions 53% of the trajectories agree with crystallized conformations in Χ(1) and Χ(2). This level of recovery is on par with Rosetta performance for the 20 natural amino acids. In addition, Rosetta predicts the distance between two spin labels with a mean error of 4.4 Å. The width of the experimental distance distribution, which reflects the flexibility of the two spin labels, is predicted with a mean error of 1.3 Å. RosettaEPR makes full-atom spin label modeling available to a wide scientific community in conjunction with the powerful suite of modeling methods within Rosetta. Public Library of Science 2013-09-05 /pmc/articles/PMC3764097/ /pubmed/24039810 http://dx.doi.org/10.1371/journal.pone.0072851 Text en © 2013 Alexander et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Alexander, Nathan S.
Stein, Richard A.
Koteiche, Hanane A.
Kaufmann, Kristian W.
Mchaourab, Hassane S.
Meiler, Jens
RosettaEPR: Rotamer Library for Spin Label Structure and Dynamics
title RosettaEPR: Rotamer Library for Spin Label Structure and Dynamics
title_full RosettaEPR: Rotamer Library for Spin Label Structure and Dynamics
title_fullStr RosettaEPR: Rotamer Library for Spin Label Structure and Dynamics
title_full_unstemmed RosettaEPR: Rotamer Library for Spin Label Structure and Dynamics
title_short RosettaEPR: Rotamer Library for Spin Label Structure and Dynamics
title_sort rosettaepr: rotamer library for spin label structure and dynamics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764097/
https://www.ncbi.nlm.nih.gov/pubmed/24039810
http://dx.doi.org/10.1371/journal.pone.0072851
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