Nucleoside triphosphates are crucial mediators of life. The high energy phosphoanhydride bond of (usually) ATP is used to drive unfavorable chemical reactions, to fuel biological machines, and to regulate a vast number of processes via phosphorylation of proteins. GTP, in turn, is used almost exclusively for the regulation of signal transduction and transport processes, whereas the other nucleotides play a less important role, except in synthesis pathways involving sugars (UTP) and phospholipids (CTP) and as building blocks of polynucleotides such as RNA and DNA. Proteins that bind and use these nucleotides for enzymatic reaction and regulation are very diverse. Although some of them constitute the largest protein superfamilies known (e.g. protein kinases), others seem to be far less conserved in evolution.

Many basic events which concern management and manipulation of genes within a cell – for instance transcription, replication and recombination – rely on specific interactions between proteins and nucleic acids. Such interactions are also essential for many house-keeping functions, like packing and unpacking of DNA in chromatin and assembly of ribosomes. Moreover, the details of protein–nucleic acid interplay is essential for understanding the action of viruses. The list of functional mechanisms in biology that rely on protein–DNA and protein–RNA interactions can be made much longer, but these examples represent some of the topics which motivated structural biologists to study complexes between proteins and nucleic acids as a first step beyond structure determinations of individual biomolecules.