A Topological Framework for the Identification and Classification of Spanning Triplets in RNA–Protein Complexes

Abstract Most functional RNA molecules interact with proteins. To better understand these interactions, amino acid:ribonucleotide motifs of different sizes and scales need to be classified and characterized. Although pairs of amino acids and ribonucleotides have been previously studied, structural characteristics of triplets and other higher-order spanning motifs present in RNA–protein complexes are not fully understood. This is especially significant since such motifs may act as nexus points and provide a deeper understanding of RNA–protein recognition. To advance this goal, we propose a method for the automated identification of spanning triplet motifs in the crystal structures of RNA–protein complexes using a topology-based classification and nomenclature scheme. This method is also expandable to other higher-order spanning motifs. Additionally, we investigate the frequency and composition of spanning triplet motifs present in the available crystal structures.