Nature Review Molecular Cell and Biology 23, 166 (2022).

Abstract

 “Imagination is more important than knowledge.” This Albert Einstein quote certainly applies to a study by Seeman, Rosenberg and Rich published in the Proc. Natl Acad. Sci. USA in 1976. With knowledge of the crystal structures of DNA and RNA dinucleotide miniduplexes and of transfer RNA (tRNAPhe) and with information from nucleic acids fibre diffraction studies in hand, but five years before the introduction of the first crystal structure of a DNA–protein complex, they pondered the question: how can proteins recognize specific  sequences in double-helix nucleic acids? Specifically, they considered the unique identification of the four possible base pairs A•U(T), U(T)•A, G•C and C•G by protein side chains.