Visualizing and interacting with RNA Molecules in support of RNA Tectonics

Helly Kwee, Tobias Höllerer, Luc Jaeger

(in collaboration with Scientific Visualization Group, ZIB (Konrad Zuse Institute Berlin))

3D model of RNA molecule, with phosphate backbone (gray) and secondary structure (blue)

Overview

Understanding how molecules interact leads to our ability to predict 3D structure and structural interactions. Such knowledge has applications in fields such as drug design and self-assembly of biosensors and nano-devices. Our goal is to provide a simulation environment for molecular assembly using TGS/Mercury's Amira visualization system. We aim to emulate haptic feedback using visualization constraints, allowing users to interact with molecules that conform to user specifications while obeying physical and chemical constraints.

Details

  1. RNA Secondary Structure

    2. RNA tectonics can be thought of as a Lego game, whereby artificial RNA supra-molecular architectures are constructed from natural RNA molecules that have been decomposed and reassembled. The 3-dimensional structure of natural RNA molecules obey folding rules, which in turn drive the self-assembly of tecto-RNA. Tecto-RNA are the self-assembling building blocks that generate these super-architectures.

    We are currently using AmiraMol to visualize and manipulate the 3D structure of RNA molecules, as well as predict RNA secondary structure, which can be viewed as a 2D (Fig. 1) or 3D (Fig. 2) representation:


    Fig. 1:   2D view of secondary structure

    Fig. 2:   3D view of secondary structure


  2. Automation of Molecular Alignment

    3. Lego-like construction of RNA architectures is performed in the lab, a process that can be slow and tedious. The use of software aids in speeding up this process by allowing the user to manipulate graphical models of molecular subunits-- in effect, a "virtual construction" that helps identify physically impossible conformation and hence reduces the number of possible architectures to construct in the lab. Automation of this process serves to further speed up such determinations.

    We would like to allow the user to specify certain molecular constraints (e.g. degree of allowed stereochemical movement (twists and bends of bonds), degree of contortion of the phosphate backbone, base pairs by which to align helices.) Alternatively, we would like to enable the software to perform multiple rotations and connections (as specified by the user), and then output the contortion parameters required to yield the desired molecular alignment. The user can then decide if these contortions are realistic, and hence if the resulting conformation is also reasonable and possible to produce in the lab.

    Subunit

    Unit

    Pentamer

    Fig. 3: Step-by-step construction of a pentagon-shaped molecular unit

  3. Database of Recurrent Motifs

    4. Motifs are recurrent structural characteristics of RNA, several of which have been identified and serve as possible architectural subunits. In the interest of duplicating molecules quickly, we would like to establish and be able to access a database of already-modeled tecto-RNA. This entails designing a visual representation of the motifs, and implementing a drag-and-drop interface into Amira to further facilitate combining these motifs.

References