Bioinformatics Tools Training Program

SWISS-MODEL is a web-based integrated service dedicated to protein structure homology
modelling. It guides the user in building protein homology models at different levels of complexity.
Building a homology model comprises four main steps: (i) identification of structural template(s),
(ii) alignment of target sequence and template structure(s), (iii) model-building, and (iv) model
quality evaluation.
The SWISS-MODEL Workspace (Waterhouse et al.) is a personal web-based working environment,
where several modelling projects can be carried out in parallel. Protein sequence and structure
databases necessary for modelling are accessible from the workspace and are updated in regular
intervals. Tools for template selection, model building, and structure quality evaluation.

Modelling Modes
Depending on the difficulty of the modelling task, three different types of modelling modes are
provided, which differ in the amount of user intervention: automated mode, alignment mode, and
project mode.

Automated Mode
The Automated Mode only requires the amino acid sequence or the UniProtKB accession code of
the target protein as input.

Alignment Mode
If the desired template for modelling is known and available in the SWISS-MODEL Template
Library (SMTL), a target–template alignment in either FASTA or Clustal format may be used to
start the modelling process, thereby skipping the template search.

Project Mode
n difficult modelling situations, where the correct alignment between target and template cannot be
clearly determined by sequence-based methods, visual inspection and manual manipulation of the
alignment can help improving the quality of the resulting model significantly.

Ligand Modelling
Biologically relevant ligands and cofactors are modelled using a conservative homology transfer
approach from the templates identified in the SMTL. Ligands in the SMTL are annotated either as:
(i) relevant, non-covalently bound ligand, (ii) covalent modifications, or (iii) non-functional binders
(e.g. buffer or solvent).