PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

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

Updating ModBase

SBKB [doi:10.1038/sbkb.2014.240]
Technical Highlight - January 2015
Short description: An expanded ModBase comparative protein structure database and toolkit enables insights into protein function, including determinants of HIV-1 protease specificity.

Comparative protein structure modeling predicts HIV-1 protease cleavage sites in human proteins, such as this site (orange) and a scissile bond in Lupus La protein. Pieper, U. et al. ModBase, a database of annotated comparative protein structure models and associated resources. Nucleic Acids Res. (2014). Vol. 42, D 1, pp. D336–46, by permission of Oxford University Press.

The rise in experimentally determined structures has been outpaced by a swell of protein sequence information, creating a need for robust structural prediction. ModBase is a database of annotated comparative protein structure models for protein sequences that match at least one known structure.

Sali and colleagues (PSI NYSGRC and EFI) have updated ModBase with new features and expanded structural coverage to include almost 30 million models for domains found in 4.7 million unique protein sequences. Researchers can browse existing predictions or take advantage of tools offered through the ModWeb server.

Predictions are based on the ModPipe pipeline, which identifies and aligns structures that match a given target sequence, and then builds and assesses the models. ModPipe uses Modeller, PSI-BLAST or HHBlits and HHSearch for fold assignment and target-template alignment. Associated servers enable structural alignment, loop and protein-protein interaction modeling, structural annotation of human non-synonymous single nucleotide polymorphisms and multiple-sequence and structure alignment.

New functionality includes the use of statistically optimized atomic potentials scores to assess protein loops and docking interfaces in ModPipe. AllosMod predicts conformational transitions such as allosteric changes and ligand-induced protein dynamics, and three web tools incorporate small-angle X-ray scattering (SAXS) data: AllosMod-FoXS finds conformations with best fits to SAXS profiles, FoXSDock filters protein docking models with a SAXS profile and SAXS Merge merges profiles. Pose & Rank uses statistical potential to score protein–ligand complexes.

The authors used ModPipe to identify 100 optimal targets whose structures would more than double the modelable fraction of the human α-helical transmembrane proteome. The authors also assessed the specificity of HIV-1 protease, a target for anti-retroviral drugs. HIV-1 protease cleaves the Gag and Pol polypeptides during virion maturation as well as human proteins bearing an eight–amino acid non-homologous sequence. Based on the structural features of octopeptides that are cleaved or not in vitro, they identified structural determinants of HIV-1 protease activity and generated a ModBase dataset bearing annotated models of 118 in vitro human protein targets.

Tal Nawy


  1. U. Pieper et al. ModBase, a database of annotated comparative protein structure models and associated resources.
    Nucleic Acids Res., D336-46 (2014). doi:10.1093/nar/gkt1144

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