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Automated simulatio...
Automated simulation-based membrane protein refinement into cryo-EM data
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- Yvonnesdotter, Linnea (författare)
- KTH,Tillämpad fysik,SeRC - Swedish e-Science Research Centre,Science for Life Laboratory, SciLifeLab
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- Rovšnik, Urška (författare)
- KTH,SeRC - Swedish e-Science Research Centre,Tillämpad fysik,Science for Life Laboratory, SciLifeLab
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- Blau, Christian, 1984- (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, PO Box 1031, SE-171 21 Solna, Sweden
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- Lycksell, Marie (författare)
- KTH,Science for Life Laboratory, SciLifeLab,SeRC - Swedish e-Science Research Centre,Tillämpad fysik
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- Howard, Rebecca Joy (författare)
- KTH,Tillämpad fysik,SeRC - Swedish e-Science Research Centre,Science for Life Laboratory, SciLifeLab
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- Lindahl, Erik, 1972- (författare)
- Stockholms universitet,KTH,SeRC - Swedish e-Science Research Centre,Science for Life Laboratory, SciLifeLab,Biofysik,Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, PO Box 1031, SE-171 21 Solna, Sweden,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),KTH Royal Institute of Technology, Sweden
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(creator_code:org_t)
- Elsevier BV, 2023
- 2023
- Engelska.
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 122:13, s. 2773-2781
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- The resolution revolution has increasingly enabled single-particle cryogenic electron microscopy (cryo-EM) reconstructions of previously inaccessible systems, including membrane proteins—a category that constitutes a disproportionate share of drug targets. We present a protocol for using density-guided molecular dynamics simulations to automatically refine atomistic models into membrane protein cryo-EM maps. Using adaptive force density-guided simulations as implemented in the GROMACS molecular dynamics package, we show how automated model refinement of a membrane protein is achieved without the need to manually tune the fitting force ad hoc. We also present selection criteria to choose the best-fit model that balances stereochemistry and goodness of fit. The proposed protocol was used to refine models into a new cryo-EM density of the membrane protein maltoporin, either in a lipid bilayer or detergent micelle, and we found that results do not substantially differ from fitting in solution. Fitted structures satisfied classical model-quality metrics and improved the quality and the model-to-map correlation of the x-ray starting structure. Additionally, the density-guided fitting in combination with generalized orientation-dependent all-atom potential was used to correct the pixel-size estimation of the experimental cryo-EM density map. This work demonstrates the applicability of a straightforward automated approach to fitting membrane protein cryo-EM densities. Such computational approaches promise to facilitate rapid refinement of proteins under different conditions or with various ligands present, including targets in the highly relevant superfamily of membrane proteins.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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- art (ämneskategori)
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