Download Visualization of RNA molecules using VMD

Katri Vilkman 67615R
Ilkka Koskela 77267R
Visualization of RNA molecules
using VMD
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Table of Contents
1 Introduction....................................................................................................................... 3
2 RNA structure................................................................................................................... 4
2.1 Nucleotides............................................................................................................... 4
2.2 Nucleic acids............................................................................................................. 4
2.3 RNA Secondary structures ...................................................................................... 4
2.4 Different kinds of RNA............................................................................................... 5
2.4.1 mRNA................................................................................................................ 5
2.4.2 tRNA.................................................................................................................. 5
2.4.3 rRNA ................................................................................................................. 5
2.4.4 Catalytic RNA..................................................................................................... 5
2.4.5 Double stranded RNA........................................................................................ 6
2.4.6 RNA genes......................................................................................................... 6
3 VMD................................................................................................................................. 6
3.1 Visualisation in VMD................................................................................................. 6
3.1.1 Loading a molecule............................................................................................ 6
3.1.2 Observing the molecule in the Graphics window............................................... 7
3.1.3 Changing the molecule's representation on screen........................................... 7
3.1.4 Extensions......................................................................................................... 7
3.1.5 Rendering.......................................................................................................... 8
3.1.6 Text interfaces................................................................................................... 8
4 References....................................................................................................................... 9
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1 Introduction
WwPDB (Worldwide protein data bank) maintains an extensive databank of
macromolecule structures in a standardized file format. These are available in the same
file format (.pdb). Organizations that are members of wwPDB: RCSB PDB (USA), MSDEBI (Europe), PDBj (Japan) and BMRB (USA), which joined the organization in 2006.
Although originally founded to store protein structure models, the PDB is nowadays used
to store other macromolecules as well, such as nucleic acids.
We studied the visualization of RNA (Ribonucleic acid). Molecular 3-d structure can be
viewed via .pdbs. There are several visualization programs available. Most of them are
free for academic use. So is VMD. It is made by University of Illinois. The one we used
was VMD (Visual Molecular Dynamics). We will introduce the basic structure of RNA and
this program and some of its properties.
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2 RNA structure
Ribonucleic acid (RNA) is the way to transfer
information inside the cell. RNA is a chain of
nucleotides. It slightly differs from DNA. RNA
can also contain genetic information, for
example HIV has two single stranded RNA as
its genome.
2.1
Nucleotides
Nucleotide consists of base (adenine, urasil,
cytosine, guanine), phosphate and sugar parts.
There are two different groups of bases: purines and pyrimidines. Adenine and guanine
are purines and cytosine and urasil pyrimidines. Sugar is pentose and phosphate is
bonded to its 5'-carbon. Base is bonded to pentoses 1'-carbon. RNA has urasil instead of
thymine as a base pair to adenine. It is also single-stranded in most cases, while DNA is
double-stranded. The sugar is ribose in RNA and deoxyribose in DNA.
2.2
Nucleic acids
Nucleic acids are nucleotides combined together by phosphodiester bond. Phosphates
oxygens are bonded to riboses 3'- and 5'-carbons. Nucleic acids are polymerized to
5'->3'-direction by RNA polymerase enzyme. DNA is used as a template, which is read to
3'->5' direction.
2.3
RNA Secondary structures
RNA Molecules are not linear but, much like proteins, take
complex two- and three-dimensional structures. The
secondary structures of RNA dictate the folding of the RNA
molecule and also serve as signals in, for example,
terminating RNA polymerase function. As with proteins, the
main factors in producing secondary structures are hydrogen
bonds between different sections of the molecule. The Hbonds force the polynucleotide chain to form different structures
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hairpin loop
such as hairpin loops, bulges and internal loops. The three-dimensional structure is
dependent on the nucleotide sequence; thus a specific sequence is expressed in a specific
3d structure just like the tertiary structure of proteins is dependent on the aminoacid
sequence. Indeed, some RNA molecules even exhibit enzyme-like catalytic abitilies.
2.4
Different kinds of RNA
There are six main types of RNA: messenger RNA (mRNA), ribosomal RNA (rRNA),
transfer RNA (tRNA), catalytic RNA, double stranded RNA (dsRNA) and non-coding RNA
(”RNA” genes). Each one has its own specific way to function.
2.4.1
mRNA
Messenger RNA (mRNA) is for carrying the information out of the nucleus to protein
synthesis site in the cytoplasm. In eucaryotes the strand is spliced before the
transportation.
2.4.2
tRNA
Transfer RNA is for bringing the right amino acid to polypeptide
chain. Later on the chain will become a protein. TRNA consists of
74-93 nucleotides and has sites for codon recognition and amino
acid. It belongs to non-coding RNAs. TRNA attaches to the
mRNAs codon by hydrogen bond and leaves the right amino acid
to its place.
2.4.3
rRNA
Ribosomal RNA is one part of the ribosomes, which are the
producers of proteins. There are four different kinds of rRNA
(18S, 5,8S, 28S and 5S rRNA) in eucaryotic cell. Nucleolus
synthesizes three of those. 80% of cells RNA molecules are
ribosomal RNA. Ribosome has also some protein, so belongs to
nucleoprotein group.
2.4.4
5S rRNA in VMD
Catalytic RNA
Some RNA molecules are able to catalyze chemical reactions, for example, ligation of
other RNA molecules and forming peptide bond in the ribosome.
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2.4.5
Double stranded RNA
In some viruses RNA is double stranded (dsRNA) and contains the genetic information.
2.4.6
RNA genes
RNA genes (non-coding RNA) encode RNA and wont go to the cytoplasm for protein
synthesis. Also small fractions of RNA, micro RNA, can regulate genes.
3 VMD
VMD (abbrev. Visual Molecular Dynamics) is a molecule visualisation and analysing tool
for large biological macromolecules: proteins, lipids, nucleic acids and membrane
structures. It runs on most Unix systems, Apple Mac OS X and MS Windows. In addition to
visualisation VMD's key features are visualisation of dynamic molecular data, visualisation
of volumetric data, interactive molecular dynamics simulations, molecular analysis
commands, Tcl and Python scripting languages, extendability and support for multimodal
input and various display systems. VMD is written in C++.
3.1
3.1.1
Visualisation in VMD
Loading a molecule
VMD supports most standard file formats used in biological modeling software: PDB, PSF,
and Gromacs and AMBER files. More than one molecule can be loaded on screen
simultaneously, allowing the user to compare between different molecules. Upon loading a
file, VMD receives information on each atom of the molecule and their relative distances
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and sizes, of which it is able to calculate where bonds are formed between atoms.
3.1.2
Observing the molecule in the Graphics window
Once loaded the molecule is displayed in the Graphics window. It can be rotated, scaled
and moved with mouse commands. The window contains arrows in three (X,Y,Z)
dimensions to facilitate coordination. In addition, the lights of the displayed space can be
moved and bonds can be added to or removed from between molecules.
3.1.3
Changing the molecule's representation on screen
VMD offers numerous ways to change the way a molecule is displayed. Both the colouring
and the surface of the molecule can be altered to highlight certain areas or sections of the
molecule. Using a specific naming system the user can select anything from a certain
hydrogen bond to larger
sections of
a molecule, say, a nucleotide or a
base, and edit the way they appear on
screen. This way the user is able to
easily present the wanted molecule
structure. The colours and surface
materials can also be changed to suit
the user's purpose better by, for
example, changing the hue of a colour
or switching between different surface
materials.
3.1.4
Descriptions of molecule representation styles in VMD
Extensions
VMD is easily expandable and comes
with several built-in extensions which
add a great deal to the properties of
the software. The extensions add more
features to modeling, analyzing,
simulation and, for example, provides a
possibility to browse through PDB and
STING databases. 3rd party
extensions can easily be installed in
some extention windows
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addition to built-in software. This also concerns 3rd party raytracing software; although
VMD comes with a basic rendering tool the resolution is rather poor and the emphasis is
clearly on fast rather than high quality performance.
3.1.5
Rendering
Whether the user chooses the built-in or a 3rd party raytracer program, VMD can render
both snapshot images as well as animations through Python and Tcl scripts. The renderer
produces a sequence of rendered snapshot images which can easily be transformed to an
animation using popular movie encoding systems.
3.1.6
Text interfaces
VMD can be extended beyond it's GUI features using it's text-based input systems, the Tcl
text interface and the Python interface. Tcl ( Tool command language) is a script language
featuring loops, variationals and conditionals. Tcl can be used to execute everything the
GUI offers, but it can also be used for more complex operations. VMD also has a Python
(an extensively used programming language in bio- as well as other sciences) interface
which can be used as an alternative to Tcl.
Python interface running in OSX terminal
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4 References
http://en.wikipedia.org/wiki/Image:NA-comparedto-DNA_thymineAndUracilCorrected.png
http://fi.wikipedia.org/wiki/RNA
http://en.wikipedia.org/wiki/RNA
http://www.stanford.edu/~esorin
http://www.rnabase.org
http://www.ks.uiuc.edu/Research/vmd/
http://www.rcsb.org/
http://www.lbl.gov/Science-Articles/Archive/busta-rna.html
Humphrey, W., Dalke, A. and Schulten, K., ”VMD-Visular Molecular Dynamics” J. Molec.
Graphics 1996, 14.1, 33-38
Hiltunen et al.: Galenos IV 4th edition
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