VASTERN by tyndale


 (A suite of tools for Visual Analysis of STructure – Energy Relations in Nucleic acids)

Introduction: Analysis of experimentally determined structures, both visually as well as
computationally, can provide important clues for understanding the sequence – structure
– function space of RNA molecules. Such an understanding not only forms the basis for
mining functional motifs, it can also provide important inputs for efficient structure
prediction. We are carrying out ab initio quantum chemical computations and developing
independent algorithms, tools and preprocessed databases along with a GUI for
simultaneous visualization of structure and multiple associated data. A part of the project
is supported by the DBT(“Database of Quantum Chemical Interaction Energy and
Geometric Meta Data for Noncanonical Base Pairs in Functional RNA Structures” No.

                                Structure energy database

Motivation: Need to assess the energetics of non canonical base pairings and hence their
importance with respect to their participation in structural and functional motifs.
A: Computational method:
   1. Geometry optimized by: HF/311G**
   2. Energy calculated by: MOROKUMA and MP2 methods
   3. Computation package used GAMESS
   4. Input file created by MOLDEN and Scoop program
B: Content:
   1. Complete database of analysis ready ISIS DRAW images of all possible pairings.
   2. Database of computed interaction energies with and without deformation energies
       and with RMSD information related to frozen and relaxed geometries.
C: Features:
   1. Any type of base pair and geometry combinations can be queried
   2. Overview of available information may be retrieved
   3. Computational details on each type may be efficiently queried
   4. Provides inputs for data visualization through VASTERN
   5. Provides coordinate log files for RMSD database

                   Superposition database for base pair geometries
                        Step 1 translation

                                                                              One atom superposed

                        Step 2 first rotation

                                                                                                       planes superposed

                        Step 3 second rotation

                                                                                                    ring atoms superposed

                       Superposition and
                                                   Figure 1 The three steps for superposition
                       RMSD Calculation

Motivation: The geometry of base pairs depends on backbone torsions, base stacking
energy and tertiary interactions apart from the pairing interaction. Need for evaluating the
importance of „other than pairing‟ interactions in the context of observed geometries in
RNA motifs.
A: Method:
   1. Parsing and scooping atom type, connectivity and coordinate information from
       GAMESS log files
   2. Involves one translation and two rotations
   3. Viewable PDB files generated using in-house PDB editor
B: Features:
   1. RasMol ready files of superposed base pairs
   2. Atom type information included for CPK viewing

                                                 Rapid base pair finder

                                                Adenine                         Guanine

                                          Cytosine                              Uracil

Motivation: Need for rapid identification of interacting bases along with their geometric
characteristic and for data integration and visualization through a single interface.
A: Methodology:
   1. Rapid identification of potential pairing partner using limited parameters
   2. Detailed analysis of distance, angle and torsion parameters of potential partners
       for classification of interaction type
B: Features:
   1. Fast real time processing of even very large PDB files
   2. Dynamically developing of database of processed results for rapid viewing
   3. Neat display of summary results
   4. Tabular display of parameters evaluated
   5. Parallel diagrammatic display of analysis method
   6. Provides inputs for
           a. structure energy database for energy computation
           b. integrated visualization through VASTERN
                                     Torsion processor

Motivation: Backbone torsion angles, especially pseudo torsion angles are characteristic
of motifs and useful for motif mining. Currently there are no tools for real time analysis
and graphic visualization of accurate backbone torsions of COMPLETE RNA structures.
A: Methodology:
    1. Detailed analysis of PDB format including inconsistencies arising out of legacy
       and special features.
    2. Rapid extraction and collation of coordinates of relevant atoms
    3. In-house implementation of algorithm for torsion calculation
B: Features:
    1. Easy uploading of files for analysis in addition to dynamically developing
       database of processed files
    2. Rapid graphic display of torsion values useful for outlier identification and
    3. Selective visualization of specific nucleotides of interest
    4. Back query of nucleotide details from torsion plot display
    5. Printable tabular display of all torsion angles for all or selected nucleotides

                    Visualization tool to render RNA worm in 4D
Motivation: Backbone torsion angles, especially pseudo torsion angles are characteristic
of motifs and useful for motif mining. Currently there are no tools for real time analysis
and graphic visualization of accurate backbone torsions of the complete RNA structures.
The pseudo torsion processor tool being developed here provides a 2-D analysis of the
RNA backbone structure. Our tool adds a third dimension to the tool to make it possible
to view and analyze the RNA bases in 3-D. Our tool acts as a front end graphical
interface tool for the entire “VASTERN” being developed and allows the user to view the
base pairing between the residues and also the distance separating them.
A: Methodology:
    1. Utilization of results of the pseudo torsion processor and Rapid Base pair finder
    2. Software engineering approach and development of independent modules.
B: Features:
        1. Stand Alone Tool
        2. Displays worm and its projections.
        3. Comparison of the Jmol view of the PDB molecule and the “RNA-WORM “
        4. Platform Independent
        5. Open Source Software
        6. Modular and Extensible

Related publications:

TR No: IIIT/TR/2004/11
Theoretical Studies of non-Watson-Crick Base Pairs in Double Helical Regions of
Different RNA Structures. , Bhabdyuti Sinha, Dhananjay Bhattacharyya, Abhijit Mitra
Poster presented in
     National Symposium on Cellular and Molecular Biophysics, January 14-17, 2004,
        held at National Institute of Mental Health and Neurosciences, Bangalore.
     Symposium on Bioinformatics for Genome Analysis, January 29-30, 2004,
        Organized by the Bioinformatics Centre, Bose Institute, Kolkata.
     Symposium of NMR Drug Design and Bioinformatics (NMRS 2004), February
        17-20, 2004, organized by Bose Institute & S. N. Bose National Centre for Basic
        Sciences, Kolkata
Non-canonical base pairs and higher order structures in nucleic acids: crystal structure
database analysis; Jhuma Das, Shayantani Mukherjee, Abhijit Mitra and Dhananjay
Bhattacharyya 2006 J Biomol Struct. Dyn. 241 49-162

Multimodality of Edge Interactions within Noncanonical RNA Base Pairs: a Putative
Strategy for RNA Dynamics; Dhananjay Bhattacharyya, Swati Jain, Satya Kishore,
Abhijit Mitra and Kritika Tandon
Paper presented in
     3rd RNA Group meeting RNA 06 at CCMB, November 11 – 12, 2006

TR No. IIIT/TR/2006/25
Theoretical Analysis of Non-Canonical Base Pairing Interactions in RNA Molecules
Dhananjay Bhattacharyya, Siv Chand Koripella, Abhijit Mitra, Vijay Babu Rajendran
and Bhabdyuti Sinha
Poster presented in
    International Conference in Bioinformatics INCOB 2006, December 18-20, 2006,
        New Delhi

Associated people:
Pranathi B (MSIT 2002), Bharath Reddy, Saurabh Kumar, Sarath Mohan N, Ravi Kiran,
Siv Chand K, Swarna Rekha.V, Vamshee krishna kanth, Vamshee Krishna A, Vijay
Babu, (MSIT 2003), Kiran K K, Radhika B (M Tech 2004), Swati Jain, (B Tech 2004),
Purushotam Sharma (JRF, PhD 2007), Naveena V Y (Principal mentor MSIT), Dr.
Dhananjay Bhattacharyya (External collaborator, Saha Institute of Nuclear Physics,
Kolkata), Dr. Bhabdyuti Sinha (Research Associate), Dr. Harjinder Singh, Dr. Prosenjit
Gupta and Dr. Abhijit Mitra (Faculty CCNSB)

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