3-Day Macromolecular Visualization Course
University of Massachusetts, Amherst
June 11, 13, 15, 2001 -
with Wayne Decatur and Kelcy Newell.
Chemical Engineering Computer Lab, Lederle GRC Rm. 201/203.
9:00 AM to 5:00 PM each day (break for lunch, informal coffee breaks).
Rationale: In this day of exploding bioinformatics information
from genomics and proteomics, it is ever more important to be conversant
with macromolecular three-dimensional structure, and how it relates to
protein and nucleic acid function and rational drug design. This workshop will
enable participants to find published molecular structure data, and visualize
and interpret 3D molecular structure. Participants will be enabled to
incorporate computer visualization of protein, DNA, and RNA into their
teaching and research.
Software: The central tool for this workshop is Protein Explorer
(www.proteinexplorer.org). Protein Explorer is free,
operates on Windows or Macintosh (also
linux), and is much easier to use, yet much
more powerful than RasMol. Protein Explorer has been adopted for visualization
of macromolecular 3D structure by the Protein Data Bank
Level & Pace: This workshop is designed for
educators and biological scientists familiar with basic biochemistry, but with no
previous molecular visualization software experience.
It progresses rapidly to powerful tools that will be of interest
to researchers, including specialists in protein structure and bioinformatics.
Experienced participants are encouraged to work at their own speed,
ahead of the group -- there is plenty of power in Protein Explorer to discover!
Monday June 11.
How to use Protein Explorer to visualize structural features of
proteins and nucleic acids.
Observations may be recorded on a form provided.
- Use of the mouse to rotate the molecule; clicking to identify atoms.
- Identifying and becoming familiar with the computer representations for chains, backbones, disulfide bonds, solvent, and ligands.
- Selecting, emphasizing, and hiding portions of the molecule.
- Zooming, centering.
- Backbone, trace, cartoon, stick, ball and stick, spacefill to van der Waals radii.
- Coloring by element (Corey, Pauling, Koltun color scheme).
- Coloring cartoons by secondary structure.
- Identifying the amino and carboxy termini (5', 3' ends): N->C Rainbow (Group) color scheme.
- Interpreting the distribution of hydrophobic, polar, and charged residues
(Polarity color schemes).
- Potassium channel: 1bl8. Trp prefers lipid-water interface.
- Gramicidin in a lipid bilayer:
- Coloring to distinguish A, T, G, C, U. How to distinguish DNA from RNA. (Cf. 104d)
- Coloring by disorder: temperature factor coloring.
- Protein Explorer's clickable Seq3D
- Sequence to 3D structure mapping.
- Finding all instances of one amino acid (e.g. cysteine).
- Selecting and coloring an arbitrary range of residues.
Crystallography, NMR, Finding Molecules of Interest
- Overview of origin, nature, and limitations of molecular structure data (X-ray crystallography,
nuclear magnetic resonance).
- The Protein Data Bank
- Finding molecules of interest.
Oligomers, Single Chains, & Other Information about Your Molecule
- Getting information about your molecule.
- Protein Explorer's Molecule Information Window:
- PDB File Header
- Probable Quaternary Structures (Oligomers)
- Fewer or Single Chains
- Crystal Contacts
- Model Quality (& examples of errors in published PDB files)
- RCSB's Structure Explorer.
- NCBI Entrez, PubMed
Wednesday June 13:
Introduction to homology modeling and submission of sequences.
Contact surfaces reveal noncovalent bonds.
Cation-pi interactions and salt bridges.
Coloring a 3D protein by conservation/mutation from a multiple
protein sequence alignment (MSA3D).
9:00-10:00 Homology Modeling
- Introduction to
sequences to SWISS MODEL.
10:00-17:00 Protein Explorer, continued.
- Contact surfaces. Example: Gal4 contacting DNA (1d66), showing:
- Nonspecific charge interactions at DNA backbone phosphates,
- Sequence specific recognition DNA bases by zinc finger domain of protein,
- Hydrophobic protein-protein interaction.
- Visualizing cation-pi interactions and salt bridges.
- Preferences in Protein Explorer.
- Demonstration of Protein Explorer's MSA3D.
- Building a multiple protein sequence alignment.
- Locating and coloring regions of conservation or mutation with
Protein Explorer's MSA3D.
Friday June 15:
structure searching and alignments.
Constructing models with mutations, and
- Multiple-model NMR PDB files: simulation of thermal motion.
- Morphs of conformational changes.
- Searching by structure without reference to sequence:
(Try the bacterial cell division protein 1FSZ§.)
- Aligning two or more chains or molecules, and how to view the alignment.
- The CE site
will align any two protein chains quickly and easily
(but hetero atoms are discarded).
can align anything
(one or more than one chains), selecting any subset of atoms for
the alignment (other atoms following), and retaining hetero
atoms. The results can be saved as a PDB file, but will need
manual editing to separate models with MODEL [N] and ENDMDL
records so that Protein Explorer can distinguish the models.
Gale Rhodes provides a
DeepView tutorial: click on the section Comparing Proteins.
- Modeling: mutation and
homology modeling in DeepView.
- DeepView beginners should start with the superb
Molecular Modeling for Beginners
by Gale Rhodes, Univ. Southern Maine.
Included are tutorials on
He also provides a series of exercises to assess your command of DeepView.
- Basic use of DeepView.
- Mutatiing and changing sidechain conformations.
- Using the Ramachandran plot (interactively!).
- Judging model quality.
- Comparing proteins by alignment.
- Homology modeling.
- You will probably find useful Rhodes'
Glossary of Terms from Crystallography, NMR, and Homology Modeling.
- DeepView (aka SwissPDBViewer)
www.expasy.ch/spdbv is free, and does mutations very easily. It is very
powerful but its many keystroke shortcuts and generally abbreviate documentation
make it difficult unless you use it often.
DeepView resources are indexed at
The following topics could be discussed on request, time permitting.
- Hydrogen bonds.
- The Noncovalent Bond Finder.
- Introduction to using the RasMol/Chime Command Language.
- Rolling probe surfaces and molecular electrostatic potential coloring.
- Building a web page with hyperlinks to Protein Explorer that
prespecify molecules for your teaching or research.
- Ready-to-use tutorials in Chime for teaching
- Building Chime presentation websites.
Keep in touch!
- RasMol/Molecular Visualization Freeware/Education email list:
- PDB email discussion:
- Yours truly:
firstname.lastname@example.org (But please direct questions about RasMol
or Chime or Protein Explorer to the RasMol list, first item above.)
- Collaborations are invited that use
Protein Explorer to display information about macromolecular structure,
particularly information which may be the result of your research.
Example Molecules: PDB ID Codes
(Enter codes into Bare Explorer)
For ready-made tutorials, see the
by subject/molecule name.
-Acetylcholinesterase w/ inhibitor 1vot
-Alpha hemolysin transmembrane heptamer 7ahl
*Antibody (Fab-lysozyme) 1fdl
*Antibody (intact IgG) 1igt
ATP (with double bonds)
-Calcineurin (ser/thr phosphatase)
w/ FKBP, FK506 1tco
-Calcium transporting ATPase, transmembrane
& 3 soluble domains 1eul
Crystal of NaCl
(from Young/Mehl Crystals)
-EF hand, morph
*Hemoglobin, oxy 1hho, 1hho.mmol*
*Hemoglobin, deoxy 2hhd
*Hemoglobin, sickle 1hbs
-Hemolysin ("mushroom") 7ahl
-HIV protease-inhibitor 1ohr
Lipid bilayer with gramicidin channel (theoretical
model, Crouzy et al, Biophys J 67:1370,
*Major Histocompatibility I (with virus peptide) 2vab
*Major Histocompatibility II (with virus peptide) 1dlh
-Potassium Channel 1bl8
*Ribosome w/ 3 tRNA's, mRNA 1gix,1giy
complete ribosome backbone).
-RNA Polymerase, T7 1qln
-T cell receptor 1sbb
-Transfer RNA, Phe 1tra
-Virus, rhino, intact capsid
Bock/UWisc Virus Visualization)
Virus, SV40, capsid model
(1 atom/chain, in bare Chime)
Virus, SV40 capsid assembly (Tutorial)
* See ready-to-use tutorial(s) on this molecule at the
** Get mmol files from Probable Quaternary Structures,
*** Also available on PE's Animations
§ Example 1FSZ thanks to Gabe McCool. See also his
presentation on 1FSZ in PE