PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons
E-Collection

Related Articles
Signaling: A Platform for Opposing Functions
May 2015
Protein Folding and Misfolding: It's the Journey, Not the Destination
March 2015
Molecular Portraits of the Cell
February 2015
Nuclear Pore Complex: A Flexible Transporter
February 2015
Nuclear Pore Complex: Higher Resolution of Macromolecules
February 2015
Nuclear Pore Complex: Integrative Approach to Probe Nup133
February 2015
Piecing Together the Nuclear Pore Complex
February 2015
Updating ModBase
January 2015
Transmembrane Spans
December 2014
Mining Protein Dynamics
May 2014
Novel Proteins and Networks: Assigning Function
May 2014
Cancer Networks: Predicting Catalytic Residues from 3D Protein Structures
November 2013
The Immune System: A Brotherhood of Immunoglobulins
June 2013
The Immune System: Super Cytokines
June 2013
Infectious Diseases: Targeting Meningitis
May 2013
PDZ Domains
April 2013
Protein Interaction Networks: Adding Structure to Protein Networks
April 2013
Design and Discovery: Flexible Backbone Protein Redesign
February 2013
Pocket changes
July 2012
Predictive protein origami
July 2012
Refining protein structure prediction
March 2012
Metal mates
February 2012
Devil is in the details
January 2012
Playing while you work
November 2011
Docking and rolling
October 2011
Fit to serve
October 2011
Rosetta hone
July 2011
Structure from sequence
July 2011
An easier solution for symmetry
June 2011
Solutions in the solution
June 2011
Regulating nitrogen assimilation
January 2011
Guard cells pick up the SLAC
December 2010
Alpha/Beta Barrels
October 2010
Modeling RNA structures
May 2010
Deducing function from small structural clues
February 2010
Spot the pore
January 2010
Network coverage
November 2009
GPCR modeling: any good?
August 2009
Protein modeling made easy
July 2009
Model proteins in your lunch break
April 2009
Click for cancer-protein interactions
December 2008
Modeling with SAXS
October 2008
Designing activity
September 2008

Technology Topics Modeling

Model proteins in your lunch break

PSI-SGKB [doi:10.1038/fa_psisgkb.2009.16]
Technical Highlight - April 2009
Short description: How to build yourself a three-dimensional protein model in under 2 hours.Nature Protocols 4, 1-13 (2009)

Protein structures can provide a useful guide to biochemical function and to interaction surfaces and have helped many a biologist to develop meaningful experiments to test biological function. The lack of an experimentally determined structure does not necessarily mean that no structural information is available. The technique of homology modelling can be used to build three-dimensional models of a protein using the experimentally determined structures of closely related members of the same protein family. Producing accurate models in the absence of such a template is very difficult, and at present homology modelling is the most reliable way predicting a protein's structure.

The four main steps of comparative protein structure modeling: template selection, target–template alignment, model building and model quality evaluation.

Homology modelling consists of four steps: identifying evolutionarily related proteins with known structures; aligning corresponding residues; building the three-dimensional model; and assessing the quality of the structure. If the initial model is not good enough, these steps can be cycled through until a sufficiently accurate model is achieved.

Estimating the quality of the model is vital for establishing how reliable it is. There is a clear correlation between the degree of sequence identity between the target and the model and the accuracy of the final model. As a rough guide, the core carbon backbone of models with 50% sequence identity will have a root mean square deviation of about 1.0 Å.

The free web-based software SWISS-MODEL will help you build your model. SWISS-MODEL was the first publicly available automated modelling server, although many more have been developed since. It integrates each of the four modelling steps into one workflow, so if target and template proteins have high sequence identity, you'll hardly have anything to do. At lower levels of sequence identity, you have the option of intervening manually.

Bordoli et al., part of the team behind SWISS-MODEL, provide a simple step-by-step procedure in Nature Protocols explaining how to use this service. And as a bonus they provide troubleshooting tips and worked-through examples. This will make modelling protein structures that have reasonable sequence identity a straightforward task for molecular and cell biologists seeking a structural guide. See Fig. 1

Maria Hodges

References

  1. L. Bordoli et al. Protein structure homology modelling using SWISS-MODEL workspace.
    Nature Protocols 4, 1-13 (2009). doi:10.1038/nprot.2008.197

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health