KNIME Workflows

 Assess the coverage of a database from the distribution of the distance to the nearest neighbor of each molecule in the database. List the three most similar compounds for each compound in the database. [Requires: Canvas]

 Find the most similar compounds to a sketched molecule in a database. Screen the same database against several query structures. [Requires: Canvas]

 Search a set of structures against a sketched query molecule or SMARTS patterns. Report the compounds that don't pass all the REOS filters. [Requires: Canvas]

 Cluster structures by fingerprints and inspect the clustering statistics to choose a good number of clusters. Create automatically the optimum number of clusters based on the Kelley penalty. Select diverse representatives per cluster. [Requires: Canvas]

 Pick diverse molecules from a library and inspect the structures. [Requires: Canvas]

 Identify and characterize possible ligand binding sites (allosteric sites). Generate the ligand Interaction Diagrams. [Requires: SiteMap]

 Prepare ligands with LigPrep and dock then with Glide. Inspect the poses, perform RRHO entropy calculation and post-processing with Prime MM-GBSA. Build a MLR model for trying to predict the Glide score. Generate the ligand Interaction Diagrams for some poses. [Requires: LigPrep, Glide, Prime]

 Dock ligands into multiple conformations of the binding site and report the best pose per ligand. [Requires: Glide]

 Align the binding site, and prepare PDB structures, generate the Glide grids and write them to disk. Analyze the protein-ligand complex composition and display the ligand structures in 2D. [Requires: Glide]

 Prepare and concatenate a set of co-crystallized, known active, and inactive compounds. Dock them with Glide SP and XP to compare the results using an enrichment plot and a ROC curve. Do the same comparisons after post-processing the results with Prime MM-GBSA. [Requires: Glide, LigPrep, Prime]

 Start Maestro structure exchange with KNIME server so as to perform some steps interactively in Maestro (highlighted in orange). Extract co-crystallized ligands from PDB structures. Prepare and concatenate them with known active, and inactive compounds. Compare the enrichment curves after docking and post-processing with Prime MM-GBSA. [Requires: Glide, LigPrep, Prime]

 Structure-based Virtual Screening Workflow incorporating ligand preparation, property filtering, and successive docking using different Glide modes (HTVS, SP, XP). [Requires: Glide, QikProp, LigPrep]

 Run workflows using the simplified batch execution wrapper script.

 The Chemistry external tool nodes can be used to parse a log file with basic shell commands, run Schrödinger utilities or backends with specific options. Quick form nodes can be used to create a configuration panel for this node. [Requires: Maestro, (Phase, MacroModel)]

 Ensure unique molecule titles (using the KNIME RowID or the Schrodinger dedicated node). This is useful in the context of Canvas. [Version: 2.1][Requires: Maestro, Canvas]

 The Setup Diagnosis node reports possible problems in the plugin installation and set-up. KNIME_batch.py script is run to install KNIME features and update Schrodinger extensions in an existing or new KNIME installation.

 Uses the KNIME-Maestro connector (replacing the Run Maestro 1:1 metanode) to alter some structures in the middle of a workflow, pick residues to sample in a binding site. [Requires: Prime][Keywords: Maestro commands, scripting]

 Illustrate the Output column structure options (output only, input plus output, and output replaces input). The workflow also demonstrates a potential workaround for nodes that don't have the output column structure options yet. [Requires: MacroModel, Glide]

 The Python Script nodes are used to extract ring properties, run a Macromodel conformational search with specific parameters, and measure distances between atoms for the conformer generated. It is also illustrated how to use it to run third party tools. [Version: 2.4.2][Requires: MacroModel][Keywords: Python, scripting]

 The Run maestro command node is used to alter the formal charge of some atoms defined by an ASL and for altering the structure rendering before inspection of the OPLS partial charges. [Requires: Maestro, Macromodel]

 Display structure in PyMOL. Run PyMOL commands and save the modified structures. Raytrace views and save the images. [Requires: Maestro, PyMOL][Keywords: PyMOL, visualization]

 Perform a calculation (e.g. LigPrep, QikProp) through the webservice directly from the KNIME extension node and Generic Webservice Client node.

See installation and set-up details for the webservice in the KNIME manual section 4.2 Setting up Node Execution via a Web Service.

[Version: 6.5][Requires: LigPrep, QikProp]

 Lists the latest modified workflows in the current workspace or lists workflows containing specific nodes to assist in finding and comparing workflows. Applied on the Schrodinger and KNIME.org workflow examples. [Version: 5.9][Keywords: workflows, workspace, nodes, size, date]

 Use the parameter flow variables to control command line options not exposed in configuration panel. This is illustrated for the protein preparation, Shape screening, Macromodel minimization, Molecule reader and other nodes. [Version: 2.7.4][Requires (optionally): (MacroModel, Phase, LigPrep, Prime)][Keywords: Parameter flow variables, Quick form]

 Use the Run Maestro 1:1 metanode to alter some structures in the middle of a workflow, pick residues to sample in a binding site. [Version: 4.5][Requires: Prime][deprecated]

 Libraries are created by substitution of one or several attachments on a core structure with fragments from reagent compounds. A unique identifier is assigned to each new compound. [Requires: CombiGlide]

 Prepare a system and run a Desmond MD simulation. Then some frames are extracted and analyzed in terms of hydrogen bond network and atom distance. [Requires: Desmond][Keywords: Molecular dynamics simulation, trajectory, snapshots, jobcontrol, distance, hydrogen bond, atom selection]

 Predicts ligand states with Epik and reports the ionization form matrix. Generates with LigPrep minimized ionization-tautomeric forms ready to be docked. [Version: 2.9.0][Requires: Epik, LigPrep]

 Workflow examples using only free nodes: https://www.schrodinger.com/SchrodingerKNIMEFreeNodes Chemistry external tool, Run Maestro, Run PyMOL, Workflows in the current workspace, Multiple Sequence Viewer, Semiempirical optimization. [Version: 3.0.0][Requires: only the free node plugin and a Maestro installation for some workflows]

 Run a conformational search with various methods and compare the lowest energy conformers. Parse the log file to extract relevant information. [Version: 1.7][Requires: MacroModel, ConfGen][Keywords: conformational search, parsing]

 Extract ligands from PDB structures and run ConfGen. Compare the conformations in terms of RMSD and intramolecular distance. Run the same analysis to compare two ConfGen modes. [Version: 7.5][Requires: ConfGen][Keywords: conformations, RMSD, distance, Python, rotatable bonds, analyze cocrystallized protein-ligand complexes]

 Find common pharmacophores for four ligands using hypotheses with four to seven points. Export the best hypotheses found. [Version: 1.1][Requires: Phase]

 Screen a file against one hypothesis. Prepare a set of ligands and create a Phase database. Screen this database against several hypotheses using two sets of parameters. Compare the results based on the number of hits found and inspect the hits in Maestro. [Version: 2.4.2][Requires: Phase]

 Use a co-crystallized ligand conformation as a query to screen a set of ligands based on the shape. Screen against several queries. Commands to run the workflow in batch. [Version: 4.0][Requires: Shape Screening]

 The antibody structure can be split into Fc, Fab and Fv domains. The node scans proteins for residues that are candidates for mutation and evaluate the stability and affinity of the mutated structures. Additionally, you can gain access to the latest command-line only functionalities of the tool (e.g., to control Prime loop sampling options), run affinity maturation and aggregation calculations that can be used to compare the mutants. [Version: 2.8.0 Requires: BioLuminate]

 Run the default Induced Fit Docking protocol or customize the individual stages. The visual representation of the protein-ligand complexes (molecular representation, color, mutations) can be set before displaying the results in Maestro. [Version: 3.1][Requires: Glide, Prime]

 Read a sequence, search for possible templates, look for relevant ones, build an homology model including the largest ligand and compare it to the template structure. Run a side chain sampling and a minimization of the binding site. [Version: 2.6.5][Requires: Prime]

 Extract one monomer from each of the two multimers. Align the binding sites (via the 'Align Binding Sites' node) or the whole structure (using the 'Protein Structure Alignment' node). [Version: 2.0.5][Requires: Maestro]

 Split protein multimers by chain ID and align binding sites. [Version: 5.0][Requires: Maestro]

 Protein x-ray structures are extracted from different sources and analyzed. They are aligned by structure, and the sequences are renumbered accordingly. The statistical analysis of Ramachandran angles used as alignment-free descriptors is performed as well as the selection of the most meaningful descriptors. Most significant angles are projected onto protein structure.

This workflow was developed by Marc Bianciotto at Sanofi.

[Version: 3.1.9] [Requires: Prime, Vernalis extensions and R extensions (with CircStats library). Optional: Erlwood extensions]

 Run a semi-empirical and a Jaguar optimization job. Display the ligand ESP charges in Maestro. [Version: 7.0][Requires: LigPrep, Jaguar]

 Conformers generated with MacroModel are refined with Jaguar. They are then compared in terms of geometry and Boltzmann populations. A KNIME Report designer template is used to present the results. [Requires: MacroModel, Jaguar]

 Evaluate the pKa of specified atoms using Jaguar. [5.3][Requires: LigPrep, Jaguar][Keywords: Quantum mechanics, pKa, parameter flow variables]

 Calculate the molecular orbitals and vibrational frequencies. [Version: 6.0] [Requires: LigPrep, Jaguar][Keywords: quantum mechanics, semi-empirical, parameter flow variables, quick form nodes]

 Run semi-empirical NDDO quantum chemical optimization and generate surface properties. [6.0][Requires: LigPrep, Maestro]

 Analyze a set of PDB structures (or a molecular dynamics trajectory) with SiteMap to characterize frames for possible binding sites. Performed volume clustering on each Sitemap result to produce an ensemble of binding sites. Generate receptor grids for ensemble docking with Glide.

See details in:

Exploring Protein Flexibility: Incorporating Structural Ensembles From Crystal Structures and Simulation into Virtual Screening Protocols. Osguthorpe, D. J.; Sherman, W; Hagler, A. T. J. Phys. Chem. B 2012, 116, 6952–6959

Generation of Receptor Structural Ensembles for Virtual Screening Using Binding Site Shape Analysis and Clustering. Osguthorpe, D. J.; Sherman, W; Hagler, A. T. Chem Biol Drug Des 2012; 80: 182–193

[Version: 6.1][Requires: SiteMap, Canvas, Glide][Keywords: binding site volume, clustering, docking, molecular dynamics]

 The ligands are extracted from a set of PDB protein-ligand complexes. The complexes are then prepared and a Glide grid is generated. Finally, the cocrystallized ligands are rescored or redocked and the corresponding RMSD is measured.

This workflow is derived from the work published by Paulette Greenidge from 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

[Version: 2.9.3][Requires: Glide, LigPrep]

 The Multiple Sequence Viewer is used to edit the alignment and the corresponding homology model is built. A Glide grid is generated and the binding site is analyzed. A raytrace image of the model is also created. [Version: 2.9.2][Requires: Prime, Glide, SiteMap, PyMOL][Keywords: binding site, homology modeling, grid generation]

 Prepare a set of PDB structures and identify possible binding sites with Sitemap. Generate receptor grids with Glide for each site and used to dock ligands. [Version: 5.4][Requires: SiteMap, Glide][Keywords: binding site, ensemble docking, grid generation, druggability]

 Label compounds from a single vendor. Prepare and filter compounds by various criteria.

 Illustrate how to iterate over structures in the input table with two different looper implementations. Extract the second lowest energy conformer of each molecule after a conformational search. [Version: 2.5]

 Use a loop to unpivot the data. [Version: 2.1]

 Illustrate how to use the GroupBy node in the context of the ionization form prediction over a range of pH. Various aggregation methods are used: maximum/minimum, unique count, unique concatenate, set, and list. [Version: 2.0]