Goals:
This course will prepare students to understand and
incorporate 3D macromolecular structure into their research
and teaching.
The principles of protein structure will be
reviewed, including noncovalent bonds. Structural bioinformatics
and genomics will be introduced. Students will learn what
percentage of proteins have known 3D structures, and the
importance of crystallographic models compared to homology models, or
theoretical models.
Using laptop computers, students will learn how to find 3D protein molecular models for proteins of interest, or how to construct homology models, |
and how to use the FirstGlance in
Jmol 3D visualization software
to investigate key structural
features.
Protein structure will be related to function, evolutionary conservation and multiple-sequence alignments, and drug design. Specific oligomers will be constructed and visualized. Students will learn how to prepare customized publication-quality molecular images and animations for Powerpoint slides. Each student will prepare a report, using Powerpoint slides to capture the concepts and skills they have learned. All the software is web browser-based, easy to use, works on Windows or Mac OS X, requires no installation, is free and open-source, and is expected to be available for years to come. |
Get Started |
Workshop Startup and Overview |
I.
Protein Data Bank & PDB Codes
Crystallographic Resolution Proteopedia.Org |
An electron density map at 2.5 Å resolution. |
II.
Obtaining models for molecules of interest.
Begin Powerpoint Slides. |
III.
Review of Protein Chemistry and Structure.
Introduction to Structural Bioinformatics. |
Click to see details. |
IV. FirstGlance in Jmol for exploring any macromolecule. |
V.
Introduction to Multiple Sequence Alignment (MSA) and Conservation
ConSurf Server Structure of Atomic Coordinate ("PDB") Files |
Enolase (4enl; a glycolytic enzyme) evolutionary conservation from ConSurf. Catalytic cleft is at the left. More.. | ||
Effect of mutation on protein function | Genetic consequence | Example |
Function LOST** |
CONSERVED:
mutation LOST from gene pool |
R133C* |
None |
NOT conserved:
mutation remains in gene pool |
E143?* |
* in methyl CpG binding protein 2 (MeCP2),
3c2i:
ASASPKQRRS IIRDRGPMYD DPTLPEGWTR KLKQRKSGRS AGKYDVYLIN PQGKAFRSKV ELIMYFEKVG DTSLDPNDFD FTVTGRGSPS RHHHHHH ^ ^ ** R133C causes Rett syndrome, a severe neurological disorder. Gray: disordered in crystal, absent in model 3c2i. |
VI.
FirstGlance in Jmol -- Part II
Solution NMR Isoelectric Point Intrinsically Unstructured Proteins |
VII.
Publication Quality Images and Animations with Polyview-3D
Finishing Powerpoint Questions |
Click on the above image for a larger view and explanation. |
Additional Resources.
Probably we will not have time in class to spend on these resources. Links are provided here in case you are interested to look at these later. |
Simplified SV40 Virus Capsid. |
Lac repressor bending the DNA operon. If this image is not moving, reload the page. |