ModeRNA: a tool for comparative modeling of RNA 3D structure

RNA is a large group of functionally important biomacromolecules. In striking analogy to proteins, the function of RNA depends on its structure and dynamics, which in turn is encoded in the linear sequence. However, while there are numerous methods for computational prediction of protein three-dimensional (3D) structure from sequence, with comparative modeling being the most reliable approach, there are very few such methods for RNA. Here, we present ModeRNA, a software tool for comparative modeling of RNA 3D structures. As an input, ModeRNA requires a 3D structure of a template RNA molecule, and a sequence alignment between the target to be modeled and the template. It must be emphasized that a good alignment is required for successful modeling, and for large and complex RNA molecules the development of a good alignment usually requires manual adjustments of the input data based on previous expertise of the respective RNA family. ModeRNA can model post-transcriptional modifications, a functionally important feature analogous to post-translational modifications in proteins. ModeRNA can also model DNA structures or use them as templates. It is equipped with many functions for merging fragments of different nucleic acid structures into a single model and analyzing their geometry. Windows and UNIX implementations of ModeRNA with comprehensive documentation and a tutorial are freely available.

[1]  R. Abagyan,et al.  Homology Modeling , 2020, Methods in Molecular Biology.

[2]  Rolf Backofen,et al.  Freiburg RNA Tools: a web server integrating IntaRNA, ExpaRNA and LocARNA , 2010, Nucleic Acids Res..

[3]  D. Baker,et al.  Atomic accuracy in predicting and designing non-canonical RNA structure , 2010, Nature Methods.

[4]  Valentina Tozzini,et al.  Multiscale modeling of proteins. , 2010, Accounts of chemical research.

[5]  Dirk Walther,et al.  Sequence–structure relationships in RNA loops: establishing the basis for loop homology modeling , 2009, Nucleic acids research.

[6]  Eric Westhof,et al.  New metrics for comparing and assessing discrepancies between RNA 3D structures and models. , 2009, RNA.

[7]  Henri Grosjean,et al.  DNA and RNA Modification Enzymes: Structure, Mechanism, Function and Evolution , 2009 .

[8]  Bartek Wilczynski,et al.  Biopython: freely available Python tools for computational molecular biology and bioinformatics , 2009, Bioinform..

[9]  Magdalena A. Jonikas,et al.  Coarse-grained modeling of large RNA molecules with knowledge-based potentials and structural filters. , 2009, RNA.

[10]  Peter F. Stadler,et al.  tRNAdb 2009: compilation of tRNA sequences and tRNA genes , 2008, Nucleic Acids Res..

[11]  Robert D. Finn,et al.  Rfam: updates to the RNA families database , 2008, Nucleic Acids Res..

[12]  Joanna M. Kasprzak,et al.  MODOMICS: a database of RNA modification pathways. 2008 update , 2008, Nucleic acids research.

[13]  J. Maizel,et al.  RNA2D3D: A program for Generating, Viewing, and Comparing 3-Dimensional Models of RNA , 2008, Journal of biomolecular structure & dynamics.

[14]  Anna Tramontano,et al.  The Evaluation of Protein Structure Prediction Results , 2008, Molecular biotechnology.

[15]  Ronny Lorenz,et al.  The Vienna RNA Websuite , 2008, Nucleic Acids Res..

[16]  F. Major,et al.  The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data , 2008, Nature.

[17]  Helen M Berman,et al.  RNA backbone: consensus all-angle conformers and modular string nomenclature (an RNA Ontology Consortium contribution). , 2008, RNA.

[18]  A. Carr,et al.  Smc5/6: a link between DNA repair and unidirectional replication? , 2008, Nature Reviews Molecular Cell Biology.

[19]  Eckart Bindewald,et al.  RNAJunction: a database of RNA junctions and kissing loops for three-dimensional structural analysis and nanodesign , 2007, Nucleic Acids Res..

[20]  Marek Blazewicz,et al.  RNA FRABASE version 1.0: an engine with a database to search for the three-dimensional fragments within RNA structures , 2007, Nucleic Acids Res..

[21]  D. Baker,et al.  Automated de novo prediction of native-like RNA tertiary structures , 2007, Proceedings of the National Academy of Sciences.

[22]  Alain Laederach,et al.  Informatics challenges in structured RNA , 2007, Briefings Bioinform..

[23]  R. Knight,et al.  PyCogent: a toolkit for making sense from sequence , 2007, Genome Biology.

[24]  K. Biegeleisen.  The probable structure of the protamine-DNA complex. , 2006, Journal of theoretical biology.

[25]  P. Schimmel,et al.  Two conformations of a crystalline human tRNA synthetase–tRNA complex: implications for protein synthesis , 2006, The EMBO journal.

[26]  E. Westhof,et al.  The building blocks and motifs of RNA architecture. , 2006, Current opinion in structural biology.

[27]  Robert K Z Tan,et al.  YUP: A Molecular Simulation Program for Coarse-Grained and Multi-Scaled Models. , 2006, Journal of chemical theory and computation.

[28]  John Moult,et al.  Rigorous performance evaluation in protein structure modelling and implications for computational biology , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[29]  Janusz M Bujnicki,et al.  Protein‐Structure Prediction by Recombination of Fragments , 2006, Chembiochem : a European journal of chemical biology.

[30]  Marcin Feder,et al.  MODOMICS: a database of RNA modification pathways , 2005, Nucleic Acids Res..

[31]  MICHAEL A. JOHNSTON,et al.  Framework‐based design of a new all‐purpose molecular simulation application: The Adun simulator , 2005, J. Comput. Chem..

[32]  J. Poehlsgaard,et al.  The bacterial ribosome as a target for antibiotics , 2005, Nature Reviews Microbiology.

[33]  Eric Westhof,et al.  Sequence to Structure (S2S): display, manipulate and interconnect RNA data from sequence to structure , 2005, Bioinform..

[34]  J. Maurice Rojas,et al.  Practical conversion from torsion space to Cartesian space for in silico protein synthesis , 2005, J. Comput. Chem..

[35]  Wouter Boomsma,et al.  Full cyclic coordinate descent: solving the protein loop closure problem in Cα space , 2005, BMC Bioinformatics.

[36]  John Moult,et al.  A decade of CASP: progress, bottlenecks and prognosis in protein structure prediction. , 2005, Current opinion in structural biology.

[37]  Adam Godzik,et al.  Fold recognition methods. , 2005, Methods of biochemical analysis.

[38]  Ruth Nussinov,et al.  ARTS: alignment of RNA tertiary structures , 2005, ECCB/JBI.

[39]  Chang-Shung Tung,et al.  Atomic model of the Thermus thermophilus 70S ribosome developed in silico. , 2004, Biophysical journal.

[40]  A. S. Krasilnikov,et al.  Basis for Structural Diversity in Homologous RNAs , 2004, Science.

[41]  Robert C. Edgar,et al.  MUSCLE: multiple sequence alignment with high accuracy and high throughput. , 2004, Nucleic acids research.

[42]  N. Bergman,et al.  The three-dimensional architecture of the class I ligase ribozyme. , 2004, RNA.

[43]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology Information: update , 2004, Nucleic acids research.

[44]  A. Goede,et al.  Loops In Proteins (LIP)--a comprehensive loop database for homology modelling. , 2003, Protein engineering.

[45]  Manuel C. Peitsch,et al.  SWISS-MODEL: an automated protein homology-modeling server , 2003, Nucleic Acids Res..

[46]  John D. Westbrook,et al.  Tools for the automatic identification and classification of RNA base pairs , 2003, Nucleic Acids Res..

[47]  H. Berman,et al.  Electronic Reprint Biological Crystallography the Protein Data Bank Biological Crystallography the Protein Data Bank , 2022 .

[48]  Zukang Feng,et al.  The Nucleic Acid Database. , 2002, Acta crystallographica. Section D, Biological crystallography.

[49]  A. Sali,et al.  Evolution and physics in comparative protein structure modeling. , 2002, Accounts of chemical research.

[50]  Z. Luthey-Schulten,et al.  Ab initio protein structure prediction. , 2002, Current opinion in structural biology.

[51]  N. Grishin.  Fold change in evolution of protein structures. , 2001, Journal of structural biology.

[52]  Konrad Hinsen,et al.  The molecular modeling toolkit: A new approach to molecular simulations , 2000, J. Comput. Chem..

[53]  Mark Gerstein,et al.  How far can sequences diverge? , 1997, Nature.

[54]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[55]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[56]  E. Westhof,et al.  Modelling of the three-dimensional architecture of group I catalytic introns based on comparative sequence analysis. , 1990, Journal of molecular biology.

[57]  Eric Westhof,et al.  Solution structure of human U1 snRNA. Derivation of a possible three- dimensional model , 1990, Nucleic Acids Res..

[58]  E Westhof,et al.  Computer modeling from solution data of spinach chloroplast and of Xenopus laevis somatic and oocyte 5 S rRNAs. , 1989, Journal of molecular biology.

[59]  A. Lesk,et al.  The relation between the divergence of sequence and structure in proteins. , 1986, The EMBO journal.

[60]  J. Havgaard,et al.  Multiple structural alignment and clustering of RNA sequences , 2007, Bioinform..

[61]  Nucleic Acids Research Advance Access published April 17, 2008 R-Coffee: a method for multiple alignment of non-coding RNA , 2007 .

[62]  Sean R. Eddy,et al.  BMC Bioinformatics BioMed Central Methodology article Efficient pairwise RNA structure prediction and alignment using sequence alignment constraints , 2006 .

[63]  BMC Molecular Biology BioMed Central Research article Comparative 3-D Modeling of tmRNA , 2005 .

[64]  BMC Bioinformatics BioMed Central Methodology article Accelerated probabilistic inference of RNA structure evolution , 2005 .

[65]  Marcin Feder,et al.  A “FRankenstein's monster” approach to comparative modeling: Merging the finest fragments of Fold‐Recognition models and iterative model refinement aided by 3D structure evaluation , 2003, Proteins.

[66]  Steven E. Brenner,et al.  SCOR: a Structural Classification of RNA database , 2002, Nucleic Acids Res..

[67]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[68]  M Gerstein,et al.  Protein evolution. How far can sequences diverge? , 1997, Nature.

[69]  C. Zwieb,et al.  Three-dimensional comparative modeling of RNA. , 1997, Nucleic acids symposium series.

[70]  B. Ganem.  RNA world , 1987, Nature.

[71]  Yaqi Wan,et al.  Predicting RNA Structure by Multiple Template Homology Modeling , 2010, Pacific Symposium on Biocomputing.

[72]  M. K. Inoue,et al.  Defining 3D residue environment in protein structures using SCORPION and FORMIGA , 2022 .

[73]  Eric Westhof,et al.  BIOINFORMATICS APPLICATIONS NOTE , 2022 .