Abstract
RNA molecules have been known to play a variety of significant roles in cells. In principle, the functions of RNAs are largely determined by their three-dimensional (3D) structures. As more and more RNA 3D structures are deposited in the Protein Data Bank (PDB), a bioinformatics tool that can quickly and accurately search the PDB database for similar RNA 3D structures or substructures is helpful to understand the structural and functional relationships of RNAs. Since its first release in 2011, R3D-BLAST has become a useful tool for searching the PDB database for similar RNA 3D structures and substructures. It was implemented by a structur-al-alphabet (SA)-based approach, which utilizes an SA with 23 structural letters to encode RNA 3D structures into 1D sequences of SA letters and applies BLAST to the SA-encoded sequences for searching similar RNA 3D substructures. In this study, we have re-implemented R3D-BLAST into a new web server named R3D-BLAST2 based on a higher quality SA newly constructed from a representative and sufficiently non-redundant list of RNA 3D structures. In addition, we have modified the kernel program in R3D-BLAST2 so that it can accept as input an RNA 3D structure in the mmCIF format. Our experimental results on a benchmark dataset have finally shown that R3D-BLAST2 indeed outperforms its previous version R3D-BLAST and other similar tools RNA FRABASE, FASTR3D and RAG-3D by searching a larger number of RNA 3D substructures similar to those of the query RNA. Therefore, we believe that R3D-BLAST2 can serve as a valuable BLAST-like search tool that can more accurately search the PDB database for similar RNA 3D substructures.