Functional protein dynamics in a crystal
Abstract Proteins are molecular machines and to understand how they work, we need to understand how they move. New pump-probe time-resolved X-ray diffraction methods open up ways to initiate and observe protein motions with atomistic detail in crystals on biologically relevant timescales. However, p...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47473-4 |
| _version_ | 1797199343563833344 |
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| author | Eugene Klyshko Justin Sung-Ho Kim Lauren McGough Victoria Valeeva Ethan Lee Rama Ranganathan Sarah Rauscher |
| author_facet | Eugene Klyshko Justin Sung-Ho Kim Lauren McGough Victoria Valeeva Ethan Lee Rama Ranganathan Sarah Rauscher |
| author_sort | Eugene Klyshko |
| collection | DOAJ |
| description | Abstract Proteins are molecular machines and to understand how they work, we need to understand how they move. New pump-probe time-resolved X-ray diffraction methods open up ways to initiate and observe protein motions with atomistic detail in crystals on biologically relevant timescales. However, practical limitations of these experiments demands parallel development of effective molecular dynamics approaches to accelerate progress and extract meaning. Here, we establish robust and accurate methods for simulating dynamics in protein crystals, a nontrivial process requiring careful attention to equilibration, environmental composition, and choice of force fields. With more than seven milliseconds of sampling of a single chain, we identify critical factors controlling agreement between simulation and experiments and show that simulated motions recapitulate ligand-induced conformational changes. This work enables a virtuous cycle between simulation and experiments for visualizing and understanding the basic functional motions of proteins. |
| first_indexed | 2024-04-24T07:14:15Z |
| format | Article |
| id | doaj.art-85c2f1b509a344db9a4623ebe5f0d76d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T07:14:15Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-85c2f1b509a344db9a4623ebe5f0d76d2024-04-21T11:24:02ZengNature PortfolioNature Communications2041-17232024-04-0115111310.1038/s41467-024-47473-4Functional protein dynamics in a crystalEugene Klyshko0Justin Sung-Ho Kim1Lauren McGough2Victoria Valeeva3Ethan Lee4Rama Ranganathan5Sarah Rauscher6Department of Physics, University of TorontoDepartment of Physics, University of TorontoDepartment of Ecology and Evolution, University of ChicagoDepartment of Chemical and Physical Sciences, University of Toronto MississaugaDepartment of Chemical and Physical Sciences, University of Toronto MississaugaCenter for Physics of Evolving Systems and Department of Biochemistry and Molecular Biology, University of ChicagoDepartment of Physics, University of TorontoAbstract Proteins are molecular machines and to understand how they work, we need to understand how they move. New pump-probe time-resolved X-ray diffraction methods open up ways to initiate and observe protein motions with atomistic detail in crystals on biologically relevant timescales. However, practical limitations of these experiments demands parallel development of effective molecular dynamics approaches to accelerate progress and extract meaning. Here, we establish robust and accurate methods for simulating dynamics in protein crystals, a nontrivial process requiring careful attention to equilibration, environmental composition, and choice of force fields. With more than seven milliseconds of sampling of a single chain, we identify critical factors controlling agreement between simulation and experiments and show that simulated motions recapitulate ligand-induced conformational changes. This work enables a virtuous cycle between simulation and experiments for visualizing and understanding the basic functional motions of proteins.https://doi.org/10.1038/s41467-024-47473-4 |
| spellingShingle | Eugene Klyshko Justin Sung-Ho Kim Lauren McGough Victoria Valeeva Ethan Lee Rama Ranganathan Sarah Rauscher Functional protein dynamics in a crystal Nature Communications |
| title | Functional protein dynamics in a crystal |
| title_full | Functional protein dynamics in a crystal |
| title_fullStr | Functional protein dynamics in a crystal |
| title_full_unstemmed | Functional protein dynamics in a crystal |
| title_short | Functional protein dynamics in a crystal |
| title_sort | functional protein dynamics in a crystal |
| url | https://doi.org/10.1038/s41467-024-47473-4 |
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