PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Protein Folding and Misfolding: It's the Journey, Not the Destination
March 2015
CCR5 and HIV Infection
January 2015
HIV/AIDS: Pre-fusion Env Exposed
January 2015
HIV/AIDS: Slide to Enter
January 2015
Updating ModBase
January 2015
Power in Numbers
August 2014
Quorum Sensing: A Groovy New Component
August 2014
Bacterial CDI Toxins
June 2014
Immunity: One Antibody to Rule Them All
June 2014
Virology: A Bat Influenza Hemagglutinin
March 2014
Virology: Making Sensitive Magic
March 2014
Virology: Visualizing Cyanophage Assembly
March 2014
Virology: Zeroing in on HBV Egress
March 2014
March 2014
Cas4 Nuclease and Bacterial Immunity
February 2014
Microbial Pathogenesis: A GNAT from Pseudomonas
February 2014
Microbial Pathogenesis: Targeting Drug Resistance in Mycobacterium tuberculosis
February 2014
Microbiome: The Dynamics of Infection
September 2013
Membrane Proteome: A Funnel-like Viroporin
August 2013
Infectious Diseases: A Pathogen Ubiquitin Ligase
May 2013
Infectious Diseases: A Shared Syringe
May 2013
Infectious Diseases: Determining the Essential Structome
May 2013
Infectious Diseases: Targeting Meningitis
May 2013
NDM-1 and Antibiotics
May 2013
Bacterial Hemophores
January 2013
Microbial Pathogenesis: Computational Epitope Prediction
January 2013
Microbial Pathogenesis: Influenza Inhibitor Screen
January 2013
Microbial Pathogenesis: Measles Virus Attachment
January 2013
Microbial Pathogenesis: NEAT Iron
January 2013
Membrane Proteome: Sphingolipid Synthesis Selectivity
December 2012
A signal sensing switch
September 2012
Gauging needle structure
July 2012
Anthrax Stealth Siderophores
June 2012
A Pseudomonas L-serine dehydrogenase
May 2012
Pilus Assembly Protein TadZ
April 2012
Making Lipopolysaccharide
January 2012
Superbugs and Antibiotic Resistance
December 2011
A change to resistance
November 2011
An effective and cooperative dimer
November 2011
The Perils of Protein Secretion
November 2011
Bacterial Armor
October 2011
Breaking down the defenses
September 2011
Moving some metal
August 2011
Capsid assembly in motion
April 2011
Know thy enemy … structurally
October 2010
Treating sleeping sickness
May 2010
Bacterial spore kinase
April 2010
Hemolysin BL
January 2010
Unusual cell division
October 2009
Anthrax evasion tactics
September 2009
Toxin-antitoxin VapBC-5
September 2009
Antibiotic target
August 2009
July 2009
Tackling influenza
June 2009
You look familiar: the Type VI secretion system
June 2009
Unique SARS
April 2009
Anthrax stealth molecule
March 2009
A new class of bacterial E3 ubiquitination enzymes
January 2009
Antiviral evasion
October 2008
SARS connections
September 2008
SARS Coronavirus Nonstructural Protein 1
June 2008

Research Themes Infectious diseases

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