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We illustrate that the Ca 2+ -bound and apo states of subtilisin have different fluctuograms and that intra-protein communication proceeds intermittently both in space and in time. ... The mechanism of intra-protein communication and allosteric coupling is key to understanding the structure-property relationship of protein function. ... Correlate fluctuograms with co-evolution The fluctuograms of Ca 2+ -bound and apo subtilisin illustrate the mechanism of intra-protein communication and show that residues surviving from random mutagenesis ...doi:10.1371/journal.pcbi.1002023 pmid:21455286 pmcid:PMC3063751 fatcat:3dnuvifezbhprmcvrvsnkkffia