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10.1101/2020.10.15.340455

http://scihub22266oqcxt.onion/10.1101/2020.10.15.340455
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suck abstract from ncbi


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pmid33083802      bioRxiv 2020 ; ä (ä): ä
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  • Progressive and accurate assembly of multi-domain protein structures from cryo-EM density maps #MMPMID33083802
  • Zhou X; Li Y; Zhang C; Zheng W; Zhang G; Zhang Y
  • bioRxiv 2020[Oct]; ä (ä): ä PMID33083802show ga
  • Progress in cryo-electron microscopy (cryo-EM) has provided the potential for large-size protein structure determination. However, the solution rate for multi-domain proteins remains low due to the difficulty in modeling inter-domain orientations. We developed DEMO-EM, an automatic method to assemble multi-domain structures from cryo-EM maps through a progressive structural refinement procedure combining rigid-body domain fitting and flexible assembly simulations with deep neural network inter-domain distance profiles. The method was tested on a large-scale benchmark set of proteins containing up to twelve continuous and discontinuous domains with medium-to-low-resolution density maps, where DEMO-EM produced models with correct inter-domain orientations (TM-score >0.5) for 98% of cases and significantly outperformed the state-of-the-art methods. DEMO-EM was applied to SARS-Cov-2 coronavirus genome and generated models with average TM-score/RMSD of 0.97/1.4A to the deposited structures. These results demonstrated an efficient pipeline that enables automated and reliable large-scale multi-domain protein structure modeling with atomic-level accuracy from cryo-EM maps.
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