Comparative Modeling with Modeller

The program Modeller from the Sali Lab models the structure of a protein, given an alignment of its sequence with the sequence of at least one known related structure. This process is known as comparative modeling or homology modeling. The sequence to be modeled is the target, and a structure whose sequence is aligned to the target can be used as a modeling template.

Chimera provides a graphical interface to running Modeller, either locally or via a Web service hosted by the UCSF RBVI. Choosing Structure... Modeller Tools from the Multalign Viewer menu shows the interface. As a trade-off for simplicity, it is limited to a subset of the calculations that Modeller can perform; for example, only a single protein chain or subunit can be modeled at a time.

Use of Modeller, whether downloaded or via Web service, requires a license key. Academic users can register free of charge to receive a license key. (Commercial entities and government research labs, please see Modeller licensing.) Modeller 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.
See also: Model Loops, Build Structure, Rotamers, Multalign Viewer, fetching ModBase files

There are several ways one could generate the needed inputs for comparative modeling.

Individual sequences and sequence alignments in Chimera are shown in Multalign Viewer. The Modeller interface can be started by choosing Structure... Modeller Tools from the Multalign Viewer menu. Settings:

OK starts the calculation and dismisses the panel, while Apply starts the calculation without dismissing the panel. Close dismisses the panel without performing any calculation. Help brings up this manual page in a browser window.

Running Modeller is a background task. Clicking the information icon in the Chimera status line will bring up the Task Panel, in which the job can be canceled if desired.

After the calculation has finished, the comparative models are opened in Chimera and can be saved in the usual ways. The models are automatically superimposed onto the template (or the lowest-numbered of multiple templates) using matchmaker defaults, and the view is focused on that template. Model-associated information is shown in a Model List, the same dialog used for comparative models fetched from ModBase.

Running Modeller with identical inputs on different machines may give different (but equally valid) results, due to small numerical differences that can lead to finding different local optima of the modeling objective function.

UCSF Computer Graphics Laboratory / January 2012