Swiss-model (stylized as SWISS-MODEL) is a
structural bioinformatics web-server dedicated to
homology modeling
Homology modeling, also known as comparative modeling of protein, refers to constructing an atomic-resolution model of the "''target''" protein from its amino acid sequence and an experimental three-dimensional structure of a related homologous pr ...
of 3D protein structures.
, homology modeling is the most accurate method to generate reliable three-dimensional protein structure models and is routinely used in many practical applications. Homology (or comparative) modelling methods make use of experimental protein structures (templates) to build models for evolutionary related proteins (targets).
Today, Swiss-model consists of three tightly integrated components: (1) The Swiss-model pipeline – a suite of software tools and databases for automated protein structure modelling,
(2) The Swiss-model Workspace – a web-based
graphical user interface
A graphical user interface, or GUI, is a form of user interface that allows user (computing), users to human–computer interaction, interact with electronic devices through Graphics, graphical icon (computing), icons and visual indicators such ...
workbench,
(3) The Swiss-model Repository – a continuously updated database of homology models for a set of model organism proteomes of high biomedical interest.
Pipeline
Swiss-model pipeline comprises the four main steps that are involved in building a homology model of a given protein structure:
# Identify structural template(s).
BLAST and
HHblits are used to identify templates. Those are stored in the Swiss-model Template Library (SMTL), which is derived from
Protein Data Bank
The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules such as proteins and nucleic acids, which is overseen by the Worldwide Protein Data Bank (wwPDB). This structural data is obtained a ...
(PDB).
#
Align target sequence and template structure(s).
# Build model and minimize energy. Swiss-model implements a rigid fragment assembly approach in modelling.
# Assess model quality using QMEAN, a statistical potential of mean force.
Workspace
The Swiss-model Workspace integrates programs and databases required for
protein structure prediction
Protein structure prediction is the inference of the three-dimensional structure of a protein from its amino acid sequence—that is, the prediction of its Protein secondary structure, secondary and Protein tertiary structure, tertiary structure ...
and modelling in a web-based workspace. Depending on the complexity of the modelling task, different modes of use can be applied, in which the user has different levels of control over individual modelling steps: automated mode, alignment mode, and project mode. A fully automated mode is used when a sufficiently high
sequence identity between target and template (>50%) allows for no human intervention at all. In this case only the sequence or
UniProt
UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived fro ...
accession code of the protein is required as input. The alignment mode enables the user to input their own target-template alignments from which the modelling procedure starts (i.e. search for templates step is skipped and rarely only minor changes in the provided alignment are made). The project mode is used in more difficult cases, when manual corrections of target-template alignments are needed to improve the quality of the resulting model. In this mode the input is a project file that can be generated by the DeepView (Swiss Pdb Viewer) visualization and structural analysis tool,
to allow the user to examine and manipulate the target-template alignment in its structural context. In all three cases the output is a pdb file with atom coordinates of the model or a DeepView project file.
The four main steps of homology modelling may be repeated iteratively until a satisfactory model is achieved.
The Swiss-model Workspace is accessible via the
ExPASy web server, or it can be used as part of the program DeepView (Swiss Pdb-Viewer). As of September 2015 it has been cited 20000 times in scientific literature, making it one of the most widely used tools for protein structure modelling. The tool is free for academic use.
Repository
The Swiss-model Repository provides access to an up-to-date collection of annotated three-dimensional protein models for a set of model organisms of high general interest. Model organisms include
human
Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...
,
mouse
A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...
,
C.elegans,
E.coli, and various pathogens including
severe acute respiratory syndrome coronavirus 2
Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...
(SARS-CoV-2). Swiss-model Repository is integrated with several external resources, such as
UniProt
UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived fro ...
,
InterPro,
STRING
String or strings may refer to:
*String (structure), a long flexible structure made from threads twisted together, which is used to tie, bind, or hang other objects
Arts, entertainment, and media Films
* ''Strings'' (1991 film), a Canadian anim ...
,
and Nature
Protein Structure Initiative (PSI) SBKB.
New developments of the Swiss-model expert system feature (1) automated modelling of
homo-oligomeric assemblies; (2) modelling of essential metal ions and biologically relevant ligands in protein structures; (3) local (per-residue) model reliability estimates based on the QMEAN local score function;
(4) mapping of
UniProt
UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains a large amount of information about the biological function of proteins derived fro ...
features to models. (1) and (2) are available when using the automated mode of the Swiss-model Workspace; (3) is always provided when calculating an homology model using the Swiss-model Workspace, and (4) is available in the Swiss-model Repository.
Accuracy and reliability of the method
In the past, the accuracy, stability and reliability of the Swiss-model server pipeline was validated by the
EVA-CM benchmark project. , the Swiss-model server pipeline is participating in the Continuous Automated Model EvaluatiOn (
CAMEO3D) project, which continuously evaluates the accuracy and reliability of protein structure prediction services via fully automated means.
References
External links
* {{Official website, swissmodel.expasy.org
See also
*
Homology modelling
*
Protein structure prediction
Protein structure prediction is the inference of the three-dimensional structure of a protein from its amino acid sequence—that is, the prediction of its Protein secondary structure, secondary and Protein tertiary structure, tertiary structure ...
*
Protein structure prediction software
This list of protein structure prediction software summarizes notable used software tools in protein structure prediction, including homology modeling, protein threading, ''ab initio'' methods, Protein structure prediction#Secondary structure, se ...
*
CASP
Critical Assessment of Structure Prediction (CASP), sometimes called Critical Assessment of Protein Structure Prediction, is a community-wide, worldwide experiment for protein structure prediction taking place every two years since 1994. CASP pro ...
(Critical Assessment of Techniques for Protein Structure Prediction)
Bioinformatics
Molecular modelling software