Conformational and connotational heterogeneity: A surprising relationship between protein structural flexibility and puns

Protein structures are often thought of as static objects, and indeed, the bulk of a protein's sequence forms α‐helices, β‐sheets, and other generally well‐ordered substructures. These portions of the molecule pre‐pay the entropic price of maintaining a globally unique fold, freeing other regions to adopt multiple alternative conformations. In many cases, this localized flexibility is biologically interesting: it may be important for catalytic turnover or for conformational selection before forming an intermolecular complex, for example. Similarly, most of written language is carefully tuned to avoid ambiguity and convey a singular meaning, a cohesive message. This linguistic scaffolding in some sense pre‐pays a rhetorical price, paving the way for punctuated instances in which a given word or phrase can simultaneously adopt multiple alternative connotations—in other words, for puns. Proteins 2015; 83:797–798. © 2015 Wiley Periodicals, Inc.