The modeller command runs Modeller on a web service hosted by the UCSF RBVI, or using a local installation specified with executableLocation.
For running the web service, a Modeller license key must be specified with the licenseKey command option or entered in the Modeller Comparative or Model Loops dialog, but this only has to be done once; the key is saved in the preferences.
Modeller is developed by the Šali Lab, and its users should cite:
Comparative protein modelling by satisfaction of spatial restraints. Šali A, Blundell TL. J Mol Biol. 1993 Dec 5;234(3):779-815.
The corresponding graphical tool is Modeller Comparative. The following are required for each target chain:
Modeling a multimer requires a multimeric template structure with the same stoichiometry and expected spatial relationship. Modeller uses this stoichiometry and spatial relationship rather than trying to calculate it.
The target sequence can be fetched from UniProt or opened from a file. That single sequence suffices as the “alignment” if the template is similar enough in sequence to associate with it (see an example). Alternatively, a multiple sequence alignment of the target and template(s) can be opened from a file, if available, or obtained by using the blastprotein command to search for templates with the target sequence as a query.
Modeling a heteromultimer requires a separate sequence alignment for each unique chain. For example, modeling an α2β2 tetramer requires a template structure that is also a α2β2 tetramer with its two α subunits associated with one alignment containing the target α sequence, and its two β subunits associated with another alignment containing the target β sequence.
With the above requirements and license key in place, the only mandatory command argument per target is the sequence-spec. For example, the following command specifies the next-to-last sequence in the alignment super8.msf as the target:
modeller comp super8.msf:-2 multichain true num 3 het true
Templates are not specified in the command. All of the structure chains associated with any sequence in the same alignment as the target will be used as templates. For an example of modeling a heterodimer, see the ChimeraX Modeller highlight.
The corresponding graphical tool is Model Loops. Missing segments can be built de novo, or existing segments refined by generating additional possible conformations. The following are required:
The target sequence can be taken from the structure metadata (and shown for a specific chain using the menu: Tools... Sequence... Show Sequence Viewer), or fetched from UniProt, or opened from a file. The sequence must be the same as the sequence of the structure, except that differences are permitted within the segments to be filled in or refined, as well as any adjacent positions designated as flexible; the residue types shown in the Sequence Viewer will be used to model those segments. Accuracy can be quite high for shorter loops, but falls off rapidly with length (>50% poor predictions for segments with 10+ residues including the flexible positions, see Table 1 in Fiser et al., Protein Sci. 9(9):1753 (2000)).
modeller refine 1/X:1:67-72 1/V:1:84,103 adjacent 2
modeller loops 1/A:1:all adjacent 0 num 3
When results are returned, the new models are opened, listed in the Model Panel along with any other models present in ChimeraX, and automatically superimposed on the lowest-model-ID template structure with matchmaker. Scores are shown in a Modeller Results panel.
Additional scores can be obtained from the SaliLab Model Evaluation Server using the Modeller Results dialog or the modeller scores command. (Any atomic model can be “evaluated” with this command, but in the absence of a Modeller Results dialog to show the scores, the only result will be to assign them as model attributes.)
For comparative or loop modeling:numModels N
Number of models to create (default 5, maximum 1000).licenseKey key
Use of Modeller requires a license key, but it only has to be specified once in ChimeraX; the key is saved in the preferences. Academic users can register free of charge to receive a license key. Commercial entities and government research labs, please see Modeller licensing.block true | false
Whether to wait for the calculation to finish before starting to execute any subsequent commands, default true when the modeller command is being executed in a command script and/or in nogui mode, otherwise false.directory inputs-directory
Specify a location for automatically generated input files, where inputs-directory is either the pathname of an existing directory (folder), or the word browse to specify it interactively in a file browser window. If this option is not used, the files will be placed in a temporary system directory that will be removed when no longer needed. This option allows users to retain the input files for examination or other purposes.executableLocation executable
Specify running a local installation of Modeller instead of the RBVI-hosted web service, where executable is either the pathname of the executable or the word browse to specify it interactively in a file browser window. The local installation must be version 10 or newer.
For comparative modeling only:multichain true | false
Whether to retain template homomultimeric states (default true); for example, if the template structure is a homotrimer, whether to model the target as a homotrimer instead of as a monomer with three templates.fast true | false
Whether to use fast/approximate mode (~3 times faster) to get a rough idea of model appearance or to confirm that the alignment is reasonable (default false). This mode does not randomize the starting structure (generates only a single model) and performs very little optimization of the target function.hetPreserve true | false
Whether to include HETATM residues other than water (ligands, ions, detergent, etc.) from templates in the output models (default false). Any such residues not desired in the output should be deleted from the template(s) beforehand if the option is turned on.waterPreserve true | false
whether to include water residues from templates in the output models (default false). Any water residues not desired in the output should be deleted from the template(s) beforehand if the option is turned on.hydrogens true | false
Whether to include hydrogen atoms in the output models (default false); increases computation time by approximately a factor of 4.
For loop modeling only:adjacentFlexible N
How many additional residues at each end of the missing segment or specified region to remodel relative to the input structure (zero or an integer, default 1). If the residues designated as flexible are different types in the sequence than in the structure, the residue types in the sequence will be used.chains chain-spec
Limit the calculation to the specified chains (e.g., when multiple structure chains are associated with the same sequence).protocol standard | DOPE | DOPE-HR
Which loop-modeling protocol to use: standard (default) or Discrete Optimized Protein Energy score (DOPE, see Shen and Sali, Protein Sci 15:2507 (2006)) with Lennard-Jones potential and GB/SA implicit solvent interaction. The DOPE protocol generally gives higher-quality results but is more computationally expensive and more prone to calculation failure, potentially resulting in fewer models than requested. DOPE-HR is the same as DOPE, except with higher precision.
refresh true | false
The refresh option applies to modeller scores only and specifies whether to overwrite existing scores (default false, do not overwrite existing scores). Refreshing scores may be useful after models have been modified (for example, to delete untemplated regions built as extended tails). However, since re-evaluation does not use all of the same information as does scoring during the original modeling process, it may worsen pre-existing GA341 and zDOPE scores and should only be used after making modifications that are expected to improve the scores.