PROTIEN EXPLORER

1
PROTIEN EXPLORER

• Sana Bashir

2
Protein Explorer

• Protein Explorer is a protein visualization
  software. Strictly speaking, "molecular
  visualization" means looking at a structure
  without changing it.
• The resulting "model" comes straight from the PDB
  file.

3
RasMol

• Protein Explorer is a RasMol-derivative software
  developed by Eric Martz
• In 1989, Roger Sayle became interested in the
  problem of depth perception for computer
  representations of solid objects. His goal was to
  write a shadowing program (ray-tracing algorithm)
  fast enough to allow rotating the shadowed image.
  He managed to write the second fastest
  sphere-shadowing program in the world!
• This algorithm was implemented in RasMol as well
  as Protein Explorer

4
Ray tracing

• Ray tracing is a method of generating realistic
  images by computer, in which the paths of
  individual rays of light are followed from the
  viewer to their points of origin.
• The algorithm begins by shooting a ray from the
  eye and through the screen, determining all the
  objects that intersect the ray, and finding the
  nearest of those intersections. It then recurses
  (or repeats itself) by shooting more rays from
  the point of intersection to see what objects are
  reflected at that point, what objects may be seen
  through the object at that point, which light
  sources are directly visible from that point, and
  so on.

5
Ray tracing (continued)

• As the ray travels from the eye, it intersects A,
  is subsequently reflected to B, then reflected to
  C, and so on.
• Ray tracer calculates the angle at which the ray
  should bounce off, and then create another ray
  that will travel from the point of intersection
  in the calculated direction. Once that ray
  figures what color it needs to be (by calculating
  all the intersecting objects, finding the nearest
  one, and determining the surface color at the
  point), the first ray is then given that color.
  This is then propagated back to the pixel through
  which the original ray was fired.
• In this case, D is transparent, and the light is
  bent both on entering the sphere, and again on
  exiting it

6
Ray tracing (continued)

• The ray travels from the eye to where it
  intersects with sphere A. In order to determine
  whether there is a shadow at that point, one
  shadow ray is fired at each light source. The
  shadow ray from A to the second light source
  travels uninterrupted, so light reaches the point
  from that light source. However, sphere B lies
  between sphere A and light source 1, so the
  point is in shadow with respect to that light
  source. The intensity of color at that point on
  sphere A would represent the fact that only one
  of the two light sources is shining directly on
  that point.

7
Why create Protein Explorer?

• Need for a software more efficient than RasMol in
  the following
• maximally informative
• illustrated introductions to computer renderings
  such as clicking on any atom to identify it
• More powerful rendering options
• context-triggered help
• user friendly interface for novice as well as
  advanced
• MDL's Chime - a visualizer in the form of a
  Netscape Navigator plug-in. Chime uses an
  adaptation of the rendering and command-language
  from RasMol. About 16,000 lines of RasMol source
  code were converted to C, made reentrant, and
  built into Chime

8
Background

• Older versions dealt with compatibility issues
  with Windows, Macintosh OS. As well as problems
  loading PDB files and running command script
  files
• Beta 1.98 included Protein Comparator,
  discontinued in later versions. Unable to load
  PDB files directly from the Protein Data Bank

9
Background (continued)

• New Version
• Can create MolSlides (molecular structures that
  user generates). MolSlides display in a web
  browser, without Protein Explorer, from your
  computer or from a server, on-line.
• MolSlide Manager
• Compatibility with Netscape 7, Mozilla, Firefox
  browsers
• You don't need to learn any hand-typed commands
  to achieve a very high level of visualization
  power.

10
Protein Structure Rendering

• PE cannot show you a protein if all you have is
  the amino acid sequence, needs atomic coordinates
  from the PDB file.
• Most macromolecular structures are determined
  experimentally by X-ray crystallography. However,
  if 3D structure is not available. A reasonably
  reliable structure can be predicted by homology
  modeling.
• PE does not support homology modeling  

11
Protein Explorer Functionality

• Protein Explorer enables you to see the relations
  of 3D molecular structure to function. The image
  can be simplified by hiding everything except the
  region of interest. A variety of one-click
  renderings and color schemes help to visualize
  the backbone, secondary structure, distributions
  of hydrophobic vs. hydrophilic residues,
  noncovalent bonding interactions, and protein
  comparison

12
PE Comparator Function

• A function of PE that provides side-by-side
  comparison of two molecules (PDB files) with all
  the same capabilities as the one-molecule
• Currently working on implementing in new version
  directly via browser.

13
Same or Different?
14
Non-covalent bonds

• In PDB files, you will not see the noncovalent
  bonds between neighboring molecules in a protein
  crystal
• At present, PE can display as rods connecting
  atoms only two subsets of hydrogen bonds protein
  backbone-to-backbone h-bonds within chains (but
  not between chains), and Watson-Crick h-bonds
  between DNA base pairs. PE presently has no
  built-in routines to show h-bonds between
  backbone and sidechain, backbone and water,
  sidechain and sidechain, sidechain and water,
  protein and ligand, protein and nucleic acid,
  non-canonical h-bonds in DNA or RNA, etc.
  However, manual methods are available to show
  arbitrary bonds.

15
How to use?

• Go to protienexplorer.org
• Install MDL Chime
• Click on quick start button, it will
  automatically open up the software with a protein
  given

16
Control Panel control to explore the structure
Molecular Image 3D view of protien
Message Frame identity of specific atom,chains,
amino acid residues
17
PE Feature Limitations

• Visualize a molecule given only a sequence of
  amino acids and nucleotides
• There is visualization but there are no modeling
  capabilities in PE.
• Cannot generate new molecular structures or
  modify old ones
• Build, mutate bonds in a structure
• No Docking, It is not possible to load multiple
  PDB files into Chime, nor move molecules relative
  to each other in a single Chime image. Two
  molecules can be displayed side by side in
  Protein Comparator, and moved together in
  synchrony or independently. Two molecules can be
  aligned and displayed together, but cannot be
  moved relative to each other.
• Saving the state of your PE session is
  problematic. You can save a command script to
  play back later, but this is technically
  challenging. A script recorder is under
  development to help this situation.

18
PE Limitations (continued)

• The positions of covalent bonds may be shown
  incorrectly. Some strong bonds may not be shown
  as rods (especially involving metals, or between
  hetero atoms and protein or nucleic acid), or
  occasionally bond rods may be shown where only
  noncovalent bonds exist.
• Only a very limited subset of hydrogen bonds can
  be shown easily.
• There is no Undo capability yet.
• Images are not always high enough quality.
• Cylinders are not available as a cartoon
  rendering for alpha helices.

19
Technical Limitations

• PE requires the free but closed-source MDL Chime
  plug-in
• The Sequence and Seq3D displays show nonstandard
  residues as gaps
• There are some rare PDB files that PE does not
  handle correctly.
• When certain states are changed with manually
  issued commands, or from Chime's menu, related
  buttons may lose track of the status of the
  image.
• Some records do not appear in MolSlides

20
Future Implementations

• PE-Jmol? In the long term, attempts to port PE to
  use the Jmol java applet instead of MDL Chime.
  Jmol is free, has an open-source licence and
  development team, and operates on a wider range
  of platforms and browsers than does MDL Chime.
• Plan to connect PE to a server that will provide
  a PDB file suitable for displaying all contacts
  (including non-covalently bonded atoms) to the
  asymmetric unit for any crystallographic PDB
  file.
• A mechanism to locate and display all hydrogen
  bonds, including buttons to show categories such
  as backbone-backbone, backbone-sidechain,
  sidechain-sidechain, interchain, water bridges.

21
References

• Protein Explorer 2.79 Beta
• E. Martz, Protein Explorer Easy Yet Powerful
  Macromolecular Visualization, Trends in
  Biochemical Sciences 27 (2002) 107-109.
• Protein Explorer (Chime) http//www.umass.edu/micr
  obio/chime/pe_beta/pe/protexpl/frntdoor.htm
• RasMol Protein Explorer http//www2.uah.es/biomo
  del/pe/1/protexpl/pe_v_ras.htm
• Chime http//www.umass.edu/microbio/chime/