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Protein Modeling 101

An educational resource about protein structure modeling

Please click on the graphical flowchart to select chapters of interest:

img Structure and Template Libraries Protein Sequence Databases Homology / Comparative Modelling Tools De novo structure prediction tools Hybrid techniques Template selection / fold recognition Model validation and quality estimation Hybrid methods Structure visualization Molecular Interactions Molecular motions

Homology Modeling Tools

Homology modeling (or comparative modeling) aims to build three-dimensional protein structure models using experimentally determined structures of related family members as templates. Please find here a (non exhaustive) list of homolgy modeling tools and services:

  • HHpred: Server for homology detection and structure prediction by HMM-HMM comparison.
  • I-Tasser: I-TASSER is a server for protein structure and function predictions. 3D models are built based on multiple-threading alignments by LOMETS and iterative TASSER assembly simulations.
  • M4T: Comparative Modelling using a combination of multiple templates and iterative optimization of alternative alignments.
  • Modeller: Software for homology or comparative modeling of protein three-dimensional structures. MODELLER implements comparative protein structure modeling by satisfaction of spatial restraints.
  • ModWeb: A web server for automated comparative modeling that relies on PSI-BLAST, IMPALA and MODELLER.
  • SWISS-MODEL: Fully automated protein structure homology-modeling server accessible via the ExPASy web server, or from the program DeepView (Swiss Pdb-Viewer).

De novo prediction Tools

In cases where no suitable template structure can be identified, de novo (a.k.a. ab initio) structure prediction methods can be used to generate three-dimensional protein models without relying on a homologus template structure:

  • Robetta: Full-chain protein structure prediction server based on the Rosetta method.
  • Rosetta: De novo protein structure prediction software.

Hybrid techniques

The goal of hybrid techniques is to contribute to a comprehensive structural characterization of biomolecules ranging in size and complexity from small peptides to large macromolecular assemblies. Detailed structural characterization of assemblies is generally impossible by any single existing experimental or computational method. This barrier can be overcome by hybrid approaches that integrate data from diverse biochemical and biophysical experiments:

  • IMP: software for a comprehensive structural characterization of biomolecules.

Validation and Quality estimation Tools

Model quality assessment tools are used to estimate the reliability of predicted protein structure models. The accuracy of individual models may vary significantly from the expected average quality due for instance to suboptimal target-template alignments, low template quality, structural flexibility or inaccuracies introduced by the modeling program. Individual assessment of each model is therefore essential. Please find here a (non exhaustive) list of tools and services:

  • ModEval: Model Evaluation Server, an evaluation tool for protein structure models.
  • ModFOLD: Model Quality Assessment Server.
  • QMEAN: Server for model quality estimation.