Q. There are several experimental structures for the target I’m interested in studying. I’d like to prepare all of these structures for inspection before running a virtual screen against the ensemble of structures. Can KNIME help with this?
A. The Preprocess PDB codes workflow – which is available in your default installation of Maestro – takes as its input a list of PDB codes that you provide and automatically downloads and prepares these PDB structures with the same settings.
When you access this KNIME Workflow through the Maestro interface, you will see two options exposed in the start-up panel: Preprocess and Full preparation. The Preprocess option applies the standard defaults exposed in the Protein Preparation Wizard’s “Import and Process” tab at the “Preprocess the Workspace Structure” section. The Full Preparation option carries out the steps in the Wizard’s Refine tab, in addition to the steps included with the Preprocess option. You can easily expose additional parameters for the preparation process, such as “Fill in missing side chains using Prime” by making a minor edit to the KNIME workflow.
As with any automated procedure, we recommend visually inspecting all automatically prepared structures before using those structures for docking. In particular, be sure to check the predicted ligand ionization and tautomeric form used to optimize the binding site.
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Q. I’d like to simplify specific tasks I have to do repeatedly in Maestro, for instance, splitting up homomultimers and aligning the chains so that I can analyze them within a same coordinate frame. How can KNIME help with this?
A. The Split and Align Multimers workflow, available to be run in Maestro, was designed to assist with this common task. This workflow extracts each chain of the system into new, separate Project Table entries and then aligns those chains using Prime’s Align Binding Site tool.
This workflow can easily be extended to create Glide grids from each of those monomers, and then run cross-docking jobs using those grids.
This workflow is easily accessible in Maestro GUI and, by reducing the number of mouse clicks, makes this kind of process less error prone.
Fig. 1: The Split and Align multimers workflow is shown overlaid on the Maestro interface. A multimer, colored by chain, is shown in the Maestro Workspace adjacent the Split and Align multimers panel in Maestro, which can be used to execute the KNIME workflow.
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