9 The SWISS-MODEL server

The aim of the Internet-based SWISS-MODEL server is to provide a comparative protein modelling tool independent from expensive computer hardware and software.

The SWISS-MODEL server is reachable on the World Wide Web (WWW) and requests can be submitted through easy to fill forms. Since protein modelling is heavily dependent on the alignment between target and template sequences, SWISS-MODEL provides four distinct modes of function accessible through separate forms:

1. The First Approach Mode: This mode allows the user to submit a sequence or its Swiss-Prot identification code. In this mode, SWISS-MODEL will go through the complete procedure described above. The First Approach Mode also allows the user to define a choice of pre-selected template structures, thereby overruling the automated selection procedure. The results of the modelling procedure will be returned to the user via E-mail.
2. The Optimise Mode allows the user to re-compute a model by submitting altered sequence alignments and ProMod command files. The sequence alignment procedure, which is fully automatic in the First Approach Mode, may yield sub-optimal alignments and consequently lead to erroneous models. The automated alignment of moderately similar sequences is indeed often imprecise and the boundaries of non-conserved loops are frequently ill defined and miss-aligned. These regions of the sequence alignments must therefore be corrected by hand in order to overcome these weaknesses. The Optimise Mode allows the user to do such corrections, and to request the remodelling of the sequence by submitting his own sequence alignment. This is best done by preparing a modelling request within the Swiss-PdbViewer (see chapter 12). These requests can then be saved as "HTML" files and then submitted through a Web browser.
3. The Combine Mode allows the user to combine independently modelled protein chains in a quaternary complex, based on an existing assembly template. In the current version of the server, this assembly template must be a PDB file containing the desired protein complex. The server provides detailed guidelines on how to submit requests to this particular facility. The actions taken by the server include a superposition of each modelled chain onto its respective counterpart on the assembly template and an energy minimisation of the whole complex.
4. The GPCR Mode. To get a GPCR sequence modelled, the first step consists of selecting a template for comparative modelling from the list of available ones. These have been created a priori using the methodology described in chapter 7. Then the user types (or uses a "cuts and pastes" function) to introduce the sequences of the seven trans-membrane helices, along with an E-mail address, a contact name, and a title for the request. The SWISS-GPCR modelling pages provide detailed help in Hypertext format, links to other sites relevant to seven trans-membrane receptors, and a demonstration version of a filled in form. Furthermore, the user may query a special index of all GPCR sequences in the SWISS-PROT database, and search their sequences using a BLAST interface (Altschul et al, 1990). This allows GPCR sequences to be searched rapidly, and will also tell the user which of the available templates is the most appropriate one on which to model the query sequence. The current version of the SWISS-MODEL server does not allow the user to create a new template using his own experimental data. This can however be achieved upon direct contact with Pawel Herzyk at York.

The SWISS-MODEL Web interface provides help and guidelines to the use of the difference server modes.