Characterization of Protein Flexibility Using Small-Angle X-Ray Scattering and Amplified Collective Motion Simulations
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Large-scale flexibility within a multidomain protein often plays an important role in its biological function. Despite its inherent low resolution, small-angle x-ray scattering (SAXS) is well suited to investigate protein flexibility and determine, with the help of computational modeling, what kinds of protein conformations would coexist in solution. In this article, we develop a tool that combines SAXS data with a previously developed sampling technique called amplified collective motions (ACM) to elucidate structures of highly dynamic multidomain proteins in solution. We demonstrate the use of this tool in two proteins, bacteriophage T4 lysozyme and tandem WW domains of the formin-binding protein 21. The ACM simulations can sample the conformational space of proteins much more extensively than standard molecular dynamics (MD) simulations. Therefore, conformations generated by ACM are significantly better at reproducing the SAXS data than are those from MD simulations.
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Simulations combined with experiments revealed details of the conformational ensemble of T4 lysozyme.
“A combination of simulations and experiments revealed details of the conformational ensemble of the T4L.223–224”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [223]
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- Authors
- Wen, B., Peng, J., Zuo, X., Gong, Q., & Zhang, Z.
- Affiliations
- University of Science and Technology of China (CN)
- Argonne National Laboratory (US)
- Corresponding author
- Zhang, Zhiyong
- Venue
- Biophysical Journal
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 107
- Issue
- 4
- Pages
- 956-964
- ISSN
- 0006-3495 (ISSN-L)
- PMC
- PMC4142251
- OpenAlex
- W2071623887
- Cited by
- 20
- References
- 59
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 3
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biophysical Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Advanced Physical and Chemical Molecular Interactions
- Keywords
- protein flexibility, multidomain proteins, small-angle X-ray scattering, conformational sampling, bacteriophage T4 lysozyme, WW domain, protein conformational space
- MeSH terms
- Carrier Proteins, Computer Simulation, Elasticity, Models, Molecular, Motion, Muramidase, Nuclear Proteins, Protein Conformation, Proteins, X-Ray Diffraction, RNA-Binding Proteins, Bacteriophage T4, Scattering, Small Angle, Molecular Dynamics Simulation
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