10.
RASMOL and Molecular visualization
The amino acid sequence in a given protein molecule
determines the structure or the conformation of that particular protein. Protein
conformation in turn determines the function of that particular protein. So,
with the conformation or structure predicted, the function of any unknown
protein can also be predicted with similarity search techniques. The
relationship between sequence and function is primarily concerned with
understanding the 3-D folding of proteins and inferring protein function from
these 3-D structures.
Predicting the structure
and thus the function shall eventually help in designing a target molecule. This
is an effective approach that’s to revolutionize the medicine, pharmacology,
chemistry, molecular biology and ecology. Molecular visualization helps the
scientists to bioengineer the protein molecules just like that. User-friendly
graphic interface makes this area of Bioinformatics a fun filled, scientific
thrill to the bioscientists.
Number
of software’s both free and commercial are available to visualize the
biomolecules. The most commonly used free software are the RASMOL, CHIME, MOLMOL
and PROTEIN EXPLORER.
RasMol
RasMol is a molecular
graphics program intended for the visualisation of proteins, nucleic acids and
small molecules. This wonderful software was developed by Roger Sayle and
donated to the public domain by the author (Roger) and his employer Glaxo
Wellcome. The standalone software can be downloaded from the RasMol homepage…
www.umass.edu/microbio/rasmol
RasMol can read files
in the following formats:
pdb (Brookhaven Protein Databank),
-mdl (MDL's MOL File Format),
mol2 (Tripos' Sybyl MOL2 Format),
xyz (MSC's XYZ format),
alchemy (Alchemy File Format)
and charmm (CHARMm File Format).
It takes input as a file containing the 3-dimensional coordinates of
the atoms in a molecular structure. Atomic coordinate file or the PDB file for a
particular protein is obtained as a result of
x-ray crystallography.
One can search and retrieve
a particular protein PDB file in the Brookheaven protein data bank (PDB),
located at… www.rcsb.org/pdb/
The PDB file downloaded
from a structure database, is by default shown in the wire frame model, when
opened through RasMol. The program also draws a representation of various types
of model (a list is found in the display menu).
The most realistic model represents each atom as a
solid sphere (hydrogen atoms are usually omitted, and the size of non-hydrogen
atoms is therefore exaggerated a little so that the space-filling properties of
groups and molecules are roughly correct).
'Ball-and-stick' models
allow you to see through the structure; atoms are represented as small spheres,
and the bonds joining them as rods.
In the 'wireframe' model
the atoms are shrunk to the points where the bonds (represented as wires) meet.
In the 'backbone' model all
the side-chains are removed, and straight rods joining the positions of the
centres of the a-carbon or phosphate atoms show the folding of the polypeptide
or nucleic acid chain.
The simplest model is a
smooth ribbon drawn through the peptide units; this may be either solid
('Ribbons') or made of parallel thin wires ('Strands').
The model can be rotated
about the x, y and z axes interactively so that all parts of the molecule can be
studied. The molecule can be made smaller or larger and in addition it is
possible to expand the viewing window up to the full size of the screen - but
the larger the picture, and the more elaborate the model, the longer it takes
the computer to calculate the appearance of the drawing.
Several colouring schemes
are available (a list is found in the colours menu next to display menu); the
four most useful are 'CPK' (carbon atoms pale grey; oxygen red, nitrogen blue
and sulphur yellow), 'group' colouring (the chain is coloured with the colour of
the rainbow, from blue a the N-terminus to red at the C- terminus; this is
useful for following the fold from one end of the chain to the other), and
'shapely' and 'amino' colours. In the former scheme, the backbone is pale grey,
and the side-chain atoms are all given a colour which depends on the size and
the polarity of the side-chain. Oxygen-containing side-chains (acids, amides,
and the hydroxy-aminoacids Ser and Thr) are various shades of red, and basic
side chains (Arg, Lys, His) blue. Hydrophobic aminoacids are mostly grey, but
Ile is dark green and Val a pale magenta. The sulphur-containing amino-acids (Cys,
Met) have muddy yellow colours, Trp is yellow and Gly, white.
The 'amino' scheme is
similar but simpler: E and D are red; K and R blue; C and M yellow; H unfaded
blue jeans; Q and N a bright green/blue; S and T orange; P flesh; I,L and V dark
green; W dark purple; Y and F a lighter purple; G and A are off-white and light
gray respectively.
The
properties of the drawing are changed either by picking items from menus with
the mouse, or by typing commands into a second window. Clicking with the mouse
on any atom will cause the atom to be identified in the second window. Drawings
can be made using selected parts of the molecule only; and it is often useful,
for example, to draw some atoms or groups with the space-filling representation
and others as wireframe or backbone. H-bonds (involving the backbone of proteins
or the bases of nucleic acids) and disulphide bonds can also be drawn, to help
show secondary structure. The program
knows how to identify
secondary structure, and so these too can be isolated and drawn differently.
Command-line
window:
Starting the RasMol will
open two windows. One with the black background
(ofcourse we can change the background colour, but the default is black)
and the other which is a Command-Line window (white).
In the windows, once RasMol
is started, the Command-Line window goes minimized and sits in the bottom of the
screen (task bar).
Move or resize the two windows, so as to see both of
them at the same time.
Now, place the mouse point
on any one of the atoms in the 3-D molecule, immediately the Command-Line window
will show the details corresponding to that particular atom (like, whats the
amino acid there, which chain it belongs to, whats the amino acid residue number
and atom number etc.,).
Lots of commands can be
executed through the Command-Line window. For example, typing color red and pressing enter will change the background to red.
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