Dear Editor,

Understanding physical protein–protein interactions (PPIs) in vivo is a major challenge in elucidating the molecular mechanisms in complex biological systems. Although many approaches, such as the yeast two-hybrid (Y2H) assay, protein fragment complementary assay (PCA), and fluorescence resonance energy transfer (FRET) assay, have been developed to assess the intensity of interaction of proteins in living cells, they have practical limitations for quantitation (Morell et al., 2009; Padilla-Parra and Tramier, 2012; Stynen et al., 2012). Nucleic acid-based technologies, such as quantitative PCR (qPCR), DNA microarray, and deep sequencing, are probably most featured with quantification, high-throughput, and cost-effective for operation. Recently, new methods of detecting biomolecular interactions have been developed based on a strategy that labels target interactions using specific nucleic acid sequences (Söderberg et al., 2006; Yu et al., 2011; Zhu et al., 2013). Here, we describe a novel method, termed protein-dimerization footprinting (PdF), for the quantitative measurement of physical PPIs in vivo by directly transcoding the signal from physical PPIs into DNA sequences.