Structural bioinformatics deals with aspects of structural biology that are best handled by computer. The topics range from databases of known structures, data handling, structure computation, modelling, manipulation of data.
In addition to the lectures students will do a number of computer "pracs" which are more in the nature of demonstrations of aspects of certain software. The software demonstrated will include: PyMol, Chimera, O, VMD, CHARMM, Modeller and the Accelrys software (Discover, Insight and Affinity).
Lecturers involved are Trevor Sewell, David Pugh, Arvind Varsani, Hugh Patterton, Kevin Naidoo, Michelle Kuttel, Muhammed Sayed and Colin Kenyon.
The ability to:
- obtain structural insights from biomolecular databases
- predict protein secondary structure
- predict the three dimensional structure of proteins which have homologue whose structure is known.
- display proteins and other biomolecules
- display and interpret experimental structural data
- dock protein models into experimentally determined maps
- The observed structure of proteins - amino acids, alpha helices, beta sheets, beta bends
- The forces that shape proteins - van der Waal's forces, charge interactions, hydrogen bonds (modelled as charge interactions), the hydrophobic effect
Force field modelling
- The concept of energy and potential functions - what the physically real ones look like and empirical fudges. The limitations of our models and how we believe we could improve things by going to QM
- Energy minimization, MD and Monte-Carlo. Normal Modes.
- Secondary structure databases, protein classification
- Structural alignment
- The ideas of David Baker
Bringing in Experimental Data
- The nature of data from NMR,EM and Xray crystallography
- Maps and resolution
- Combining modelling with experimental data
- Refinement - Refmac, CNS, real-space refinemnt
- Matching constraints in NMR
- Impact on proteomics - protein protein docking
- Impact on drug discovery - databases of small molecules - active site docking - cavity fitting - in silico screening
Representations and interactive tools
- How they are structured
- How they are accessed
- Responsibility for their maintenance
- Concept of a portal
- Examples of databases of primary and derived data, in particular the PDB
- The nature and design of structural representation tools
- The capabilities of some implementations e.g. PyMol, Chimera, VMD
||Molecular and Cell Biology, UCT
|Module description (Header):
||Structural Bioinformatics and Molecular Modelling
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||Students will be required to submit a practical write up and complete an assignment. Assignments – 100%.
Protein Topology (from the European Bioinformatics Institute)
- PDB - Database of 3-D biological macromolecular structure data
- Swissprot - protein sequence database
- Prosite - Database of protein families and domains at Expasy
- SLoop - Database of Super Secondary Fragments
- Homstrad - Homologous Structure Alignment Database
- Campass - Cambridge database of Protein Alignments organised as Structural Superfamilies
Fold recognition servers
- Fugue - FUGUE uses environment-based fold profiles that are created from structural alignments. Gap penalties are environment dependent.
- 3DPSSM - Based on sequence profiles, solvatation potentials and secondary structure.
- SAMT02 - The query is checked against a library of hidden Markov models. This is NOT a threading technique, it is sequence based.
- GenTHREADER - Combines profiles and sequence-structure alignments. A neural network-based jury system calculates the final score based on solvation and pair potentials.
- Metaserver - The structure prediction Meta Server offers a gateway to many high quality fold recognition servers and provides and infrastructure and main interface to several highly reliable consensus methods.
Protein structure & alignment analysis
Homology Modelling Servers
- MODELLER -homology or comparative modelling of protein three-dimensional structures by satisfaction of spatial restraints
- SWISS-MODEL - SWISS-MODEL is an automated comparative modelling server
- SDSC1 - Protein structure homology modeling server (San Diego, USA)
- 3D-JIGSAW - Automated system for 3D models for proteins (Cancer Research)
- WHATIF - WHAT IF Web interface: homology modelling, drug docking, electrostatics calculations, structure validation and visualisation.
- RAPPER - Restraint-based protein modelling
- HMMSTR/Rosetta - Prediction of protein structure from sequence
Predicting protein loops
- CODA - a combined algorithm for predicting protein loops
Structural validation Tools
- RAMPAGE - Structural validation by assessment of the Ramachandran plot
- PROCHECK - Checks the stereochemical quality of a protein structure, producing a number of PostScript plots analysing its overall and residue-by-residue geometry.
- WHATIF - Protein structure analysis program for mutant prediction, structure verification, molecular graphics
Molecular visualization tools
- Protein-Protein Interaction Server - The server is a tool to analyse the protein-protein interface of any protein complex. You can submit the coordinates of a protein structure of your choice and then view tables describing the nature of the protein-protein interface.
2003. "Molecular Visualisation." In Structural Bioinformatics,, 135-158. Hoboken, New Jersey, USA: Wiley-Liss.
Other useful notes
Tate (2003) Summary of some of the currently available visualisation software. In: Structural Bioinformatics