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Progressive and accurate assembly of multi-domain protein structures from cryo-EM density maps (preprint)
biorxiv; 2020.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2020.10.15.340455
ABSTRACT
ABSTRACT 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 0.97/1.4Å 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.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Language:
English
Year:
2020
Document Type:
Preprint
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