Energy landscapes from cryo-EM snapshots: a benchmarking study
Abstract Biomolecules undergo continuous conformational motions, a subset of which are functionally relevant. Understanding, and ultimately controlling biomolecular function are predicated on the ability to map continuous conformational motions, and identify the functionally relevant conformational trajectories. For equilibrium and near-equilibrium processes, function proceeds along minimum-energy pathways on one or more energy landscapes, because higher-energy conformations are only weakly occupied. With the growing interest in identifying functional trajectories, the need for reliable mapping of energy landscapes has become paramount. In response, various data-analytical tools for determining structural variability are emerging. A key question concerns the veracity with which each data-analytical tool can extract functionally relevant conformational trajectories from a collection of single-particle cryo-EM snapshots. Using synthetic data as an independently known ground truth, we benchmark the ability of four leading algorithms to determine biomolecular energy landscapes and identify the functionally relevant conformational paths on these landscapes. Such benchmarking is essential for systematic progress toward atomic-level movies of continuous biomolecular function.
- Research Organization:
- Univ. of Wisconsin, Milwaukee, WI (United States)
- Sponsoring Organization:
- National Science Foundation (NSF); USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES)
- Grant/Contract Number:
- SC0002164
- OSTI ID:
- 1922142
- Journal Information:
- Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 13; ISSN 2045-2322
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United Kingdom
- Language:
- English
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