The DOI matches its Crossref record; 95 of the 97 references it cites were found in a registry or an index.
Unraveling motion in proteins by combining NMR relaxometry and molecular dynamics simulations: A case study on ubiquitin
Open accessPublished version of a preprint
Abstract
Nuclear magnetic resonance (NMR) relaxation experiments shine light onto the dynamics of molecular systems in the picosecond to millisecond timescales. As these methods cannot provide an atomically resolved view of the motion of atoms, functional groups, or domains giving rise to such signals, relaxation techniques have been combined with molecular dynamics (MD) simulations to obtain mechanistic descriptions and gain insights into the functional role of side chain or domain motion. In this work, we present a comparison of five computational methods that permit the joint analysis of MD simulations and NMR relaxation experiments. We discuss their relative strengths and areas of applicability and demonstrate how they may be utilized to interpret the dynamics in MD simulations with the small protein ubiquitin as a test system. We focus on the aliphatic side chains given the rigidity of the backbone of this protein. We find encouraging agreement between experiment, Markov state models built in the χ1/χ2 rotamer space of isoleucine residues, explicit rotamer jump models, and a decomposition of the motion using ROMANCE. These methods allow us to ascribe the dynamics to specific rotamer jumps. Simulations with eight different combinations of force field and water model highlight how the different metrics may be employed to pinpoint force field deficiencies. Furthermore, the presented comparison offers a perspective on the utility of NMR relaxation to serve as validation data for the prediction of kinetics by state-of-the-art biomolecular force fields.
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Cites
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Cited by
Banayan, N. E., Hsu, A., Hunt, J. F., Palmer, A. G., & Friesner, R. (2024) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.4c00378 · Cited by 9
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“Back-bone amide S ² order parameters for ubiquitin were computed using the iRED method 109,110 within the Python package pyDR 111,112 , with the trajectoriesdividedinto1 µ sblocksforanalysisasrecommendedbyGu et al. 110 .”
Analytical Framework to Understand the Origins of Methyl Side-Chain Dynamics in Protein Assemblies
Zumpfe, K., Berbon, M., Habenstein, B., Loquet, A., & Smith, A. A. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.3c12620 · Cited by 6
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Extending the detectable time window of fast protein dynamics using 1HN E-CPMG
Mukhopadhyay, D., Pratihar, S., Becker, S., & Griesinger, C. (2025) · Journal of Biomolecular NMR · doi:10.1007/s10858-025-00470-1 · Cited by 3
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A steady-state approach for analysis of high-resolution relaxometry
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Breaking Down Walls: Continuous Potential Models for Internal Motions in NMR Spin Relaxation
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“…Eisenhaber et al. 96 Backbone amide S² order parameters for ubiquitin were computed using the iRED method 97,98 within the Python package pyDR, 99,100 with the trajectories divided into 1 µs blocks for analysis as recommended by Gu et al. 98 Agreement between simulated and experimental…”
Metadata
- Authors
- Champion, C., Lehner, M., Smith, A. A., Ferrage, F., Bolik-Coulon, N., & Riniker, S.
- Affiliations
- ETH Zurich (CH)
- Leipzig University (DE)
- Centre National de la Recherche Scientifique (FR)
- University of Toronto (CA)
- Corresponding author
- Riniker, Sereina
- ORCID
- Venue
- The Journal of Chemical Physics
- Publisher
- AIP Publishing
- Published
- 2024-03-11
- Volume
- 160
- Issue
- 10
- ISSN
- 0021-9606 (ISSN-L)
- 1089-7690
- OpenAlex
- W4392649013
- Cited by
- 11
- References
- 97
- Citations by year
- 2025: 8 · 2024: 3
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The Journal of Chemical Physics (publishedVersion, cc-by)
- ChemRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc-nd)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- ETH Zürich Research Collection
- Funders
- European Research Council (FET-Open call, Grant Agreement 899683 (HIRES-MULTIDYN))
- Deutsche Forschungsgemeinschaft (450148812)
- Canadian Institutes of Health Research (Postdoctoral Fellowship)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Advanced Physical and Chemical Molecular Interactions
- Keywords
- ubiquitin, protein dynamics, NMR relaxometry, molecular dynamics simulation, Markov state models, romance, force field validation, water model, side chain mobility
- MeSH terms
- Magnetic Resonance Spectroscopy, Proteins, Nuclear Magnetic Resonance, Biomolecular, Ubiquitin, Molecular Dynamics Simulation
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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