title: Topology independent comparison of RNA 3D structures using the CLICK algorithm.
abstract: RNA molecules are attractive therapeutic targets because non-coding RNA molecules have increasingly been found to play key regulatory roles in the cell. Comparing and classifying RNA 3D structures yields unique insights into RNA evolution and function. With the rapid increase in the number of atomic-resolution RNA structures, it is crucial to have effective tools to classify RNA structures and to investigate them for structural similarities at different resolutions. We previously developed the algorithm CLICK to superimpose a pair of protein 3D structures by clique matching and 3D least squares fitting. In this study, we extend and optimize the CLICK algorithm to superimpose pairs of RNA 3D structures and RNA-protein complexes, independent of the associated topologies. Benchmarking Rclick on four different datasets showed that it is either comparable to or better than other structural alignment methods in terms of the extent of structural overlaps. Rclick also recognizes conformational changes between RNA structures and produces complementary alignments to maximize the extent of detectable similarity. Applying Rclick to study Ribonuclease III protein correctly aligned the RNA binding sites of RNAse III with its substrate. Rclick can be further extended to identify ligand-binding pockets in RNA. A web server is developed at http://mspc.bii.a-star.edu.sg/minhn/rclick.html.
authors.affiliation: Bioinformatics Institute, 30 Biopolis Street, #07-01, Matrix, Singapore 138671 minhn@bii.a-star.edu.sg.
authors.forename: Minh N
authors.initials: MN
authors.lastname: Nguyen
authors.affiliation: Bioinformatics Institute, 30 Biopolis Street, #07-01, Matrix, Singapore 138671.
authors.forename: Adelene Y L
authors.initials: AY
authors.lastname: Sim
authors.affiliation: Genome Institute of Singapore, 60 Biopolis Street, Genome, #02-01, Singapore 138672.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Bioinformatics Institute, 30 Biopolis Street, #07-01, Matrix, Singapore 138671.|Indian Institute of Science Education and Research, Pune, India.
authors.forename: M S
authors.initials: MS
authors.lastname: Madhusudhan
authors.affiliation: Bioinformatics Institute, 30 Biopolis Street, #07-01, Matrix, Singapore 138671.|Department of Biological Sciences, National University of Singapore, Singapore.|School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Chandra
authors.initials: C
authors.lastname: Verma
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D019985:Benchmarking; D001665:Binding Sites; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019614:Haloarcula marismortui / Q000235:genetics / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D020407:Internet; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D012335:RNA, Ribosomal / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D012984:Software
chemical_list: D012335:RNA, Ribosomal; D043244:Ribonuclease III