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Chait reported ESI-MS results for thirteen proteins with molecular masses ranging from 5000 to 77,000 Da (Chowdhury et al., 1990a), and in 1991, this group demonstrated that ESI-MS represents an effective method for probing conformational changes of proteins in solutions, since the charge state distribution (CSD) observed in an ESI mass spectrum provides insights into the proteins solution-phase conformation (Katta and Chait, 1991)