How do I build a multi-chain homology model (multimer) with Prime v3.0 / Maestro v9.2 (Suite 2011)?

The steps that should be followed depend on whether a homo-multimer model (one in which the sequences of all chains are identical) or hetero-multimer model (one in which the chains have differing sequences) is being built.

To construct a homo-multimer model using Maestro 9.2 (Suite 2011), in the Find Homologs step of Prime, select all of the chains on which the query sequence is to be built. These chains should be in the desired positions and orientations relative to each other. In the most common situation, where these chains all originate from the same template structure, this will already be the case and nothing more need be done. After optimizing the alignments in the Edit Alignment step, go to the Build Structure step and select the Homo-multimer option under the "Model type when using multiple templates" section and click Build Model. The model that is produced will consist of the query sequence built on each of the selected templates. This model is built self-consistently, with each chain being constructed and refined in the presence of the others.

To construct a hetero-multimer model using Maestro 9.2 (Suite 2011), a separate Run is required for each unique query sequence. For each such sequence, create a new Run and select the desired template and chain on which that sequence is to be built. After optimizing the alignment in the Edit Alignment step, go to the Build Structure step, but do not build the model. Once a separate Run has been created for each unique query sequence and brought forward to the Build Structure step, click on the "Hetero-multimers" button. This will open a dialog which displays all the Runs in the current project. Select the Runs corresponding to the chains to be built, and click Start. This will create the desired hetero-multimer model, built self-consistently as in the case of homo-multimers described above.

Note that building a mixed homo-/hetero-multimer is also possible. An example of such a model would be a trimer consisting of two chains of identical sequence plus a third chain of differing sequence. While three runs could be used to construct such a model, it is also possible to create one Run which is configured to build the homo-dimer, as described above, along with a second Run configured to build the third chain. Clicking on the Hetero-multimers button and selecting those two Runs will then build the desired mixed homo-/hetero-trimer.

Keywords: Prime, homology model, multimer, multi-chain, heteromultimer, homomultimer, hetero-multimer, homo-multimer

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