Interactive Visualization of RNA and DNA Structures

The analysis and visualization of nucleic acids (RNA and DNA) is playing an increasingly important role due to their fundamental importance for all forms of life and the growing number of known 3D structures of such molecules. The great complexity of these structures, in particular, those of RNA, demands interactive visualization to get deeper insights into the relationship between the 2D secondary structure motifs and their 3D tertiary structures. Over the last decades, a lot of research in molecular visualization has focused on the visual exploration of protein structures while nucleic acids have only been marginally addressed. In contrast to proteins, which are composed of amino acids, the ingredients of nucleic acids are nucleotides. They form structuring patterns that differ from those of proteins and, hence, also require different visualization and exploration techniques. In order to support interactive exploration of nucleic acids, the computation of secondary structure motifs as well as their visualization in 2D and 3D must be fast. Therefore, in this paper, we focus on the performance of both the computation and visualization of nucleic acid structure. We present a ray casting-based visualization of RNA and DNA secondary and tertiary structures, which enables for the first time real-time visualization of even large molecular dynamics trajectories. Furthermore, we provide a detailed description of all important aspects to visualize nucleic acid secondary and tertiary structures. With this, we close an important gap in molecular visualization.

[1]  Robert M. Hanson,et al.  DSSR-enhanced visualization of nucleic acid structures in Jmol , 2017, Nucleic Acids Res..

[2]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[3]  Bruce A. Shapiro,et al.  Generating non-overlapping displays of nucleic acid secondary structure , 1984, Nucleic Acids Res..

[4]  H. Bussemaker,et al.  DSSR: an integrated software tool for dissecting the spatial structure of RNA , 2015, Nucleic acids research.

[5]  Gregory S. Couch,et al.  Nucleic acid visualization with UCSF Chimera , 2006, Nucleic acids research.

[6]  Fabrice Jossinet,et al.  Assemble2: an interactive graphical environment dedicated to the study and construction of RNA architectures , 2015, 2015 IEEE 1st International Workshop on Virtual and Augmented Reality for Molecular Science (VARMS@IEEEVR).

[7]  P. Moore,et al.  Structural motifs in RNA. , 1999, Annual review of biochemistry.

[8]  Alexander S. Rose,et al.  NGL Viewer: a web application for molecular visualization , 2015, Nucleic Acids Res..

[9]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[10]  J. Maizel,et al.  An interactive technique for the display of nucleic acid secondary structure. , 1982, Nucleic acids research.

[11]  Rupert De Wachter,et al.  RnaViz 2: an improved representation of RNA secondary structure , 2003, Bioinform..

[12]  Stefan Birmanns,et al.  GPU-accelerated visualization of protein dynamics in ribbon mode , 2011, Electronic Imaging.

[13]  Craig L. Zirbel,et al.  FR3D: finding local and composite recurrent structural motifs in RNA 3D structures , 2007, Journal of mathematical biology.

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

[15]  Xiang-Jun Lu,et al.  3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures , 2008, Nature Protocols.

[16]  R. Knight,et al.  From knotted to nested RNA structures: a variety of computational methods for pseudoknot removal. , 2008, RNA.

[17]  A. Rich,et al.  A bifurcated hydrogen-bonded conformation in the d(A.T) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Robert M. Hanson,et al.  Jmol – a paradigm shift in crystallographic visualization , 2010 .

[19]  E. Westhof,et al.  Geometric nomenclature and classification of RNA base pairs. , 2001, RNA.

[20]  Michael Zuker,et al.  Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information , 1981, Nucleic Acids Res..

[21]  Conrad C. Huang,et al.  UCSF Chimera—A visualization system for exploratory research and analysis , 2004, J. Comput. Chem..

[22]  Harry F Noller,et al.  RNA Structure: Reading the Ribosome , 2005, Science.

[23]  Ivan Viola,et al.  Visualization of Biomolecular Structures: State of the Art Revisited , 2017, Comput. Graph. Forum.

[24]  H M Berman,et al.  A standard reference frame for the description of nucleic acid base-pair geometry. , 2001, Journal of molecular biology.

[25]  M Kainosho,et al.  H···N hydrogen bond lengths in double stranded DNA from internucleotide dipolar couplings , 2001, Journal of biomolecular NMR.

[26]  Peter F. Stadler,et al.  ViennaRNA Package 2.0 , 2011, Algorithms for Molecular Biology.

[27]  Pere-Pau Vázquez,et al.  Instant Visualization of Secondary Structures of Molecular Models , 2015, VCBM.

[28]  Renzhi Cao,et al.  GMOL: An Interactive Tool for 3D Genome Structure Visualization , 2015, Scientific Reports.

[29]  Robert E. Bruccoleri,et al.  An improved algorithm for nucleic acid secondary structure display , 1988, Comput. Appl. Biosci..

[30]  R De Wachter,et al.  RnaViz, a program for the visualisation of RNA secondary structure. , 1997, Nucleic acids research.

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

[32]  John C. Hart,et al.  Sphere tracing: a geometric method for the antialiased ray tracing of implicit surfaces , 1996, The Visual Computer.

[33]  Andrew E. Torda,et al.  RNA secondary structure diagrams for very large molecules: RNAfdl , 2013, Bioinform..

[34]  Daniel Baum,et al.  Accelerated Visualization of Dynamic Molecular Surfaces , 2010, Comput. Graph. Forum.

[35]  M. Frank-Kamenetskii,et al.  Base-stacking and base-pairing contributions into thermal stability of the DNA double helix , 2006, Nucleic acids research.

[36]  I. Hofacker RNA Secondary Structure Analysis Using the Vienna RNA Package , 2003, Current protocols in bioinformatics.

[37]  Thomas Ertl,et al.  GPU-based Visualisation of Protein Secondary Structure , 2008, TPCG.

[38]  Fabrice Jossinet,et al.  S2S‐Assemble2: a Semi‐Automatic Bioinformatics Framework to Study and Model RNA 3D Architectures , 2014 .

[39]  F. Allen,et al.  The Cambridge Crystallographic Data Centre: computer-based search, retrieval, analysis and display of information , 1979 .

[40]  Howard Y. Chang,et al.  Understanding the transcriptome through RNA structure , 2011, Nature Reviews Genetics.

[41]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[42]  E. Kool,et al.  Hydrogen bonding, base stacking, and steric effects in dna replication. , 2001, Annual review of biophysics and biomolecular structure.

[43]  M. Zalis,et al.  Visualizing and quantifying molecular goodness-of-fit: small-probe contact dots with explicit hydrogen atoms. , 1999, Journal of molecular biology.

[44]  Tim Weyrich,et al.  Eurographics Symposium on Point-based Graphics (2006) Gpu-based Ray-casting of Quadratic Surfaces , 2022 .

[45]  Yann Ponty,et al.  VARNA: Interactive drawing and editing of the RNA secondary structure , 2009, Bioinform..

[46]  I. Tinoco,et al.  How RNA folds. , 1999, Journal of molecular biology.

[47]  F. Major,et al.  RNA canonical and non-canonical base pairing types: a recognition method and complete repertoire. , 2002, Nucleic acids research.

[48]  Merry Wang,et al.  Accessible virtual reality of biomolecular structural models using the Autodesk Molecule Viewer , 2017, Nature Methods.

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

[50]  F. Crick,et al.  Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid , 1953, Nature.

[51]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..

[52]  Marco Punta,et al.  Genome3D: exploiting structure to help users understand their sequences , 2015, Nucleic Acids Res..

[53]  F. Crick,et al.  Molecular structure of nucleic acids , 2004, JAMA.