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Electron Spin Echo Envelope Modulation, or ESEEM, is widely used to investigate structure of the immediate surroundings of paramagnetic species. In combination with site-specific spin labeling and selective deuterium substitution, it becomes a helpful tool to study location of proteins and small peptides within membranes, interaction of small molecules with proteins, supramolecular assemblies, water accessibility to specific regions of proteins and water penetration into membranes, protein folding and secondary structures. In this review, experimental approaches and limitations, theoretical background of the method, and recent applications are discussed.

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