Application of Homology Modeling by Enhanced Profile–Profile Alignment and Flexible-Fitting Simulation to Cryo-EM Based Structure Determination
Application of cryo-electron microscopy (cryo-EM) is crucially important for ascertaining the atomic structure of large biomolecules such as ribosomes and protein complexes in membranes. Advances in cryo-EM technology and software have made it possible to obtain data with near-atomic resolution, but...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/1977 |
| _version_ | 1797479448647303168 |
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| author | Yu Yamamori Kentaro Tomii |
| author_facet | Yu Yamamori Kentaro Tomii |
| author_sort | Yu Yamamori |
| collection | DOAJ |
| description | Application of cryo-electron microscopy (cryo-EM) is crucially important for ascertaining the atomic structure of large biomolecules such as ribosomes and protein complexes in membranes. Advances in cryo-EM technology and software have made it possible to obtain data with near-atomic resolution, but the method is still often capable of producing only a density map with up to medium resolution, either partially or entirely. Therefore, bridging the gap separating the density map and the atomic model is necessary. Herein, we propose a methodology for constructing atomic structure models based on cryo-EM maps with low-to-medium resolution. The method is a combination of sensitive and accurate homology modeling using our profile–profile alignment method with a flexible-fitting method using molecular dynamics simulation. As described herein, this study used benchmark applications to evaluate the model constructions of human two-pore channel 2 (one target protein in CASP13 with its structure determined using cryo-EM data) and the overall structure of <i>Enterococcus hirae</i> V-ATPase complex. |
| first_indexed | 2024-03-09T21:46:01Z |
| format | Article |
| id | doaj.art-7533b4f5c9ca42f984807d0cfbf6613a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:46:01Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7533b4f5c9ca42f984807d0cfbf6613a2023-11-23T20:17:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234197710.3390/ijms23041977Application of Homology Modeling by Enhanced Profile–Profile Alignment and Flexible-Fitting Simulation to Cryo-EM Based Structure DeterminationYu Yamamori0Kentaro Tomii1Artificial Intelligence Research Center (AIRC), National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, JapanArtificial Intelligence Research Center (AIRC), National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, JapanApplication of cryo-electron microscopy (cryo-EM) is crucially important for ascertaining the atomic structure of large biomolecules such as ribosomes and protein complexes in membranes. Advances in cryo-EM technology and software have made it possible to obtain data with near-atomic resolution, but the method is still often capable of producing only a density map with up to medium resolution, either partially or entirely. Therefore, bridging the gap separating the density map and the atomic model is necessary. Herein, we propose a methodology for constructing atomic structure models based on cryo-EM maps with low-to-medium resolution. The method is a combination of sensitive and accurate homology modeling using our profile–profile alignment method with a flexible-fitting method using molecular dynamics simulation. As described herein, this study used benchmark applications to evaluate the model constructions of human two-pore channel 2 (one target protein in CASP13 with its structure determined using cryo-EM data) and the overall structure of <i>Enterococcus hirae</i> V-ATPase complex.https://www.mdpi.com/1422-0067/23/4/1977cryo-EMflexible fittinghomology modelingprofile–profile alignment |
| spellingShingle | Yu Yamamori Kentaro Tomii Application of Homology Modeling by Enhanced Profile–Profile Alignment and Flexible-Fitting Simulation to Cryo-EM Based Structure Determination International Journal of Molecular Sciences cryo-EM flexible fitting homology modeling profile–profile alignment |
| title | Application of Homology Modeling by Enhanced Profile–Profile Alignment and Flexible-Fitting Simulation to Cryo-EM Based Structure Determination |
| title_full | Application of Homology Modeling by Enhanced Profile–Profile Alignment and Flexible-Fitting Simulation to Cryo-EM Based Structure Determination |
| title_fullStr | Application of Homology Modeling by Enhanced Profile–Profile Alignment and Flexible-Fitting Simulation to Cryo-EM Based Structure Determination |
| title_full_unstemmed | Application of Homology Modeling by Enhanced Profile–Profile Alignment and Flexible-Fitting Simulation to Cryo-EM Based Structure Determination |
| title_short | Application of Homology Modeling by Enhanced Profile–Profile Alignment and Flexible-Fitting Simulation to Cryo-EM Based Structure Determination |
| title_sort | application of homology modeling by enhanced profile profile alignment and flexible fitting simulation to cryo em based structure determination |
| topic | cryo-EM flexible fitting homology modeling profile–profile alignment |
| url | https://www.mdpi.com/1422-0067/23/4/1977 |
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