Ask the KNIME Expert: Cocrystallized Ligand Redocking, Multiple Sequence Viewer, and KNIME-Maestro ConnectorDr. Jean-Christophe Moziconnaci, KNIME Product Manager
Schrödinger KNIME Extensions allow scientists to prototype, validate, automate, and deploy multi-step workflows. Schrödinger’s KNIME Extensions Product Manager Jean-Christophe Mozziconacci, is dedicated to developing valuable KNIME workflows for Schrödinger users and providing guidance for efficient execution of these workflows.
Q. Can I generate a Glide grid automatically from a set of diverse PDB structures to run docking experiments?
A. Yes, the new workflow example Cocrystallized Ligand Redocking includes steps for extracting ligands from a set of PDB complexes, preparing the complexes and corresponding docking grids, then redocking, rescoring, and calculating the RMSD.
*This workflow is derived from the work published by Novartis in:
Improving Docking Results via Reranking of Ensembles of Ligand Poses in Multiple X-ray Protein Conformations with MM-GBSA. Greenidge, P. A.; Kramer, C.; Mozziconacci, J.C.; Sherman, W.; J. Chem. Inf. Model. 2014, 54(10), 2697–717
MM/GBSA binding energy prediction on the PDBbind data set: Successes, failures, and directions for further improvement. Greenidge, P. A.; Kramer, C.; Mozziconacci, J.C.; Wolf, R.M.; J. Chem. Inf. Model. 2013, 53(1), 201–9.
Figure 1. The new Real World Examples > Cocrystallized Ligand Redocking workflow illustrates how Glide grids can be automatically generated and used for redocking ligands from a set of PDB complexes. The ligands are first extracted from the PDB complexes and prepared for docking. A Glide grid is then generated for each ligand and used for redocking and rescoring, before calculating the RMSD.
Q. Is there a node to visualize and manipulate amino acid sequences?
A. The new Multiple Sequence Viewer can be used to visualize sequences or edit an alignment. This node can be incorporated into many workflows and some tasks can be automated. For a full list, see the node description and use the Command line node section. For more examples take a look at the following workflows:
- Protein Modeling – Model Building
- Real World Examples – Protein Model Building
- Nodes – MSV (for simple use cases)
Figure 2. The new Multiple Sequence Viewer node can be incorporated into various workflows to interactively edit alignments and output amino acid sequences. In this example (top) the node is used to edit an alignment using the Multiple Sequence Viewer in Maestro (bottom) before building a Prime homology model. Many common tasks can also be automated using the node configuration panel Command line node section (middle).
Q. There is a step in my workflow that requires interactivity in Maestro. Is there a way to integrate this step?
A. The KNIME-Maestro Connector node can be used to make many selection/structure changes in Maestro interactively. This node is a replacement for the old Run Maestro 1:1 metanode and several new modes have been added on top of the structure exchange (see article in the Newsletter in May 2012). These new modes include All entries, Selected entries, CombiGlide core definitions, and Residue or Atom selections (as List, Names, ASL, and SMARTS). Some Maestro commands can also be added to the Command Script section to prepare the view and automate any tasks that can be automated in Maestro. Once the change/selection is made just send the structures back to KNIME and the downstream nodes will execute. The Multiple Sequence Viewer node can also be used in this context to edit sequence/alignments. For more examples see the following workflows:
- Quantum Mechanics – Conformational Search (dihedral angle selection)
- Library Design – Library Enumeration (core attachment point selection)
- General – KNIME-Maestro Connector (residue selection, create more entries))
Figure 3. Many selection/structure changes can be made interactively in Maestro using the KNIME-Maestro Connector node (top, middle). The Command Script section of this node (bottom) can also be used to execute Maestro commands and automate many tasks within Maestro.