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Javitch, Wayne A. Hendrickson, Paul A. Slesinger, Matthias Quick, Different molecule species, or molecules in different conformational states or binding configurations may co-exist. Without resolving this heterogeneity, reconstructions are blurred, and are invalid as representations of any one physical structure. Existing, widely used approaches to resolving heterogeneity, such as Relion, are based on the assumption that the structure exists in a few discrete conformations.

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