KNIME desktop and Schrödinger extensions overview

Jean-Christophe Mozziconacci and Volker Eyrich
http://www.schrodinger.com/upload/KNIME_Overview.pdf

Schrödinger extensions• 150+ nodes:– Covering most of the Schrödinger tools
Most recent additions: Residue scanning, Prime Energy, SiteMap, PyMOL, Glide grid writer
Many take in and output sdf and pdb or mol2 on top of Maestro format
Newest nodes use the same configuration panel as Maestro (see the Residue scanning node)– Structure and data manipulation nodes (eg Split by structure, delete atoms)– GUI nodes (eg Run Maestro, Run PyMOL)– Scripting nodes: Run Maestro command, Chemistry external tool, Python nodes– Utility nodes: Setup diagnosis and workflow list

• 50+ workflow examples– Workflow page: descriptions and download the ones of interest– Whole set can be downloaded with the Suite– Many other workflow drafts available on demand

Schrödinger extensions• Tested with latest KNIME version and include the version available at the timeof the release• Parameter flow variable capability– Use the options not exposed in the configuration panels (eg command line only)– Implemented for the main nodes eg Glide, MMod (eg OPLS 2.1), Jaguar• 2D renderer– 2D coordinate generation and rendering
The default renderer can be set for Maestro columns– Can be used in the Report designer

Schrödinger extensions• More and simplified start-up options and stand-alone installation configuration in the Preferences– In $SCHRODINGER/knime start-up script– eg use a stand-alone KNIME installation, set temporary directories, the memory limit…

• KNIME menu in Maestro– Connect to KNIME mode to exchange structures with a KNIME session
KNIME-Maestro connector node (Improved in 2015-1: automatic connection/close, more modes)– Build, import, edit and run workflows from Maestro on project table data
Dynamically generated GUI to alter some parameters.

• Simplified batch execution: KNIME_batch.py– Batch command generation based on workflow annotations
Stand-alone dynamically generated GUI– Useful options eg -stderr/out• Easier installation creation and update– Using Eclipse machinery in KNIME_install.py– eg list of extensions to install, from several (zipped) update sites

Schrödinger extensions
See details in:
http://www.schrodinger.com/upload/KNIME_Overview.pdf• The new features slides:– Parameter flow variables (2014-1)– Simplified batch execution (2013, 2014-1)– Chemistry external tool node improvements– KNIME menu in Maestro (2012)– Start-up script (2012)• Workflow examples:– Labs > Parameter flow variable usage– General > Installation (KNIME_install.py scenarios)– General > Workflow list
– General > Chemistry external tool node usage– Phase > Shape screening, docking (batch execution)– 2D renderer in the report designer

Why use KNIME
Automation

Combine various Tools--

Automate repetitive tasks (especially complex / error pronetasks)--

e.g. Ensemble docking, HTS analysis

Prototyping
Test parameters-

e.g. Validate docking parameters

Documentation-

Easy debugging, interruptions, data included, inspect each step
(2D, in Maestro/PyMOL)

e.g. QM workflows

ReportingShare workflows with colleagues (also in Maestro and Seurat) Not a black box---

e.g. PDB set preparation, Ligand database preparation

Collaboration

Schrodinger and third party tools (vendor agnostic), scripts(Python, Java, shell),-Nodes for reporting results- e.g. Enrichment plotter node, pdf, tables, etc.
KNIME report designer (free), web portal (KNIME.com)

InexpensiveOverview• Organized by level:– Get started– Intermediate– Advanced functionalities• And by topics:– KNIME desktop: GUI, specificities, nodes– Schrödinger extensions: specificities, nodes• You can jump between the sections using links (marked with ► or◄). See theoverview slides.
• There are also links to use-case examples (marked with ♦).

Get started
KNIME desktop
– GUI

►

– Specificities►– Nodes►

Schrödinger extensions– Specificities– Schrödinger nodes►►► Intermediate

KNIME desktop GUI•◄

Knime.org and Knime.com• KNIME desktop• Start Knime• Create a new workflow and organize a workspace• Run a node
• Import and export workflows• Tips and tricks• Documentation

Konstanz Information Miner and Ecosystem
KNIME.org-

Leading open-source ‘pipelining/workflow’ tool
Freely available to academic and industrial researchers
KNIME Desktop, based on Eclipse http://www.knime.org
Community contributions:-

Modeling tools
Marvin sketcher
RDKit
IndigoCDKR Scripting
Erlwood
Image Processing
HCS Tools
Next Generation Sequencing
Palladian (mainly GPL3)KNIME.com Enterprise products and Services-

http://www.knime.com

Report designer (free)
KNIME team space (share workflows) and KNIME server (web portal and SOA access)
Cluster execution (scalability)
KNIME professional (support, maintenance and training)
Commercial development

KNIME Extensions
15+ Extension Providers
Extensible, cross-platform, vendor neutral:
Schrödinger, CCG, Tripos, ChemAxon/Infocom, BioSolveIT, Cresset, Dotmatics, Molecular
Discovery, Molegro…

Schrödinger Extensions- First released in 2007
- 150+ nodes-

Molecular mechanics
Molecular dynamics
Quantum mechanics
Cheminformatics
Pharmacophore modeling
Combinatorial libraries
Docking
Protein structure prediction
Structure and data manipulation- Maestro integration- Workflow execution- Structure exchange

KNIME Desktop GUI• Full screen mode
• Forget about Eclipse
specific menu items
More about:• The console ►Start KNIME• Start up KNIME:– On Linux: run $SCHRODINGER/knime– On Windows: click on the icon
– Use -data MyWorkspace to open a specific workspace– File > Switch workspace, but KNIME takes time to start up again• Workspace, workflows and workflow groups:

Create a new workflow and organize a workspace•

Under the pop-up menu of Workflow Project repository:– New KNIME workflow and New Workflow group– Copy, Paste, Delete, Move, Rename•

Drag and drop the workflows in the Workflow project repository

Run a node
• Connectors• Node status• Input and output
data tables

double click or
pop-upImport and export workflows• File > Import KNIME workflow / Export KNIME workflow
or under the pop-up menu of a Workflow Project group• Import from another workspace or an archive file (zip)• Select 1 or several workflows > export as a zip fileExclude or not the cached data from the exported fileTips and tricks• Save regularly the changes. Since KNIME 2.10 there is an auto save functionality but it isn’t on
by default.
Save while running calculations (see Preferences ►)• Multiple undo and redo apply on workflow edition (execution data lost though)• The KNIME desktop isn’t based on a client-server architecture. If you close the KNIME instance
while a calculation is running it won’t kill it nor you will be able to recover the results when
opening the workflow again.

Documentation•

Node descriptions. Also accessible from Help > Help content > Knime > Node descriptions
Type in search field and inspect the configuration panel•

Product page

http://www.schrodinger.com/KNIME-Extensions

New Features, New Features Slides, KNIME Overview•

Schrödinger KNIME manual•

Schrödinger FAQs

http://www.schrodinger.com/kb•

Workflow page (examples)

http://www.schrodinger.com/knimeworkflows/•

Schrödinger’s extensions webex•

KNIME.org– Workflow examples$SCHRODINGER/docs/knime/user_manual/kni13_user_manual.pdf

http://www.schrodinger.com/seminarprior/19/24/(preconfigured server access in KNIME explorer)– Screencast

http://www.knime.com/introduction/screencasts– Forum

http://www.knime.org/forum/

KNIME desktop GUI►• Preferences• Advanced node functionalities• Errors, warnings and Console information• Flow variables and workflow variables• Metanodes• Memory limit• Tips and tricks

KNIME desktop specificities◄• Stepwise execution• Data table column types and conversion

Stepwise execution• Only stepwise execution
Ideal to take advantage of Schrödinger’s jobcontrol infrastructure• No predefined execution order for non connected branches. Use the flow variable ports[KNIME 2.3]
• Data cached at each step
• Preferences > KNIME > Maximum working threads far all nodes• 1:1 connection between nodes (use the concatenate node to combine input flows)Data table column types and conversion• KNIME relies on strict data table column typing• Converter nodes:– Double to Int (integer), String to number, Number to string– Molecule type cast (but no Maestro conversion)– Openbabel, CDK to molecule, Molecule to CDK• In the Schrödinger extensions:– String-to-type– Molecule-to-MAE, MAE-to-Pdb, MAE-to-SD, MAE-to-Smiles, MAE-to-mol2, SD-to-smiles– Canvas object converters

Schrödinger specific cell types• Structures: Maestro, Sequence, Alignment• Several files: Glide grid, Phase Hypothesis• Desmond trajectory• Binary formats: Canvas fingerprint and matrix

Readers and writers, converters

KNIME workbench nodes• KNIME workbench nodes• Data manipulation nodes• Data exchange◄

KNIME workbench nodes• I/O nodes for reading and writing data from files and databases• Data manipulation nodes for managing the internal data tables that areused to pass information between nodes• Charting and plotting tools• Loop support, time Series, Distance matrix• Statistics and data mining nodes (Mining, Weka) such as clustering, neuralnetworks, decision trees, Lib SVM
R statistical computation• Basic chemistry-aware nodes (CDK)very limited, see Schrödinger extension nodes ►The most often used nodes for data manipulation• Row filter, Row splitter and Sorter• Column filter, Column resorter, Column combiner and Rename• Joiner (see also Schrödinger Look up and add column node ►) and Concatenate (only 2 inputs)

And also:• Java snippet, RowID and GroupBy node
• Schrödinger nodes for data manipulation►►

Data exchange• As text files: File reader and csv writer nodes• In Excel format: xls reader and xls writer nodes• Between workflows: table reader and table writer nodes• See also among the Schrödinger nodes:– Schrödinger reader and writer nodes– CSV reader (read several files)– View CSV ►KNIME workbench nodes►• KNIME.com Labs nodes• Scripting and run a third party tool
• Java snippet• RowID• Group by• Miscellaneous nodes: Interactive table, Math formula, CDK Sketcher• Plotting facilities• Looping functionalities - Basics• Model building nodes

Schrödinger extensions specificities• Canvas 2D renderer• Grouped structures in a cell
• Output column structure options• Jobcontrol tab◄

Canvas 2D renderer• Preferences > KNIME > Preferred rendererGrouped structures in a cell
• #CTs: number of structures• Set of conformations, Glide poses, Ligprep forms…
• Group and ungroup nodes, match option• Also grouped SD, mol2

Output column structure options• Input plus Output, Output replaces Input, Output only
• Extract MAE properties, Set MAE properties and delete
MAE properties nodes

CTs, columns

KNIME

new CTs and/or new columns
Set mae properties

Extract mae
properties

ReaderCTs:
Structures + properties

Delete mae
properties

Schrödinger
tools

New CTs

Writer,
MaestroOutput column structure options

Jobcontrol

Schrödinger extensions specificities• Schrödinger preferences• Start-up script options• Access to flow variables►

Schrödinger nodes◄• Schrödinger node repository• Configuration panel visual coherence• Nodes of general use:
– Readers and converters– Run Maestro and Run Maestro command– Structure manipulation– Data manipulation and viewers– Scripting• KNIME workflow webpage

Access to Schrödinger tools via KNIME•••

Run on Linux, Mac and Windows
32 and 64 bit
Add our extensions to an existing KNIME
installation using the update site
150+ nodes covering the whole
Schrödinger Suite
Molecular Mechanics- MacroModel Single Point Energy- MacroModel Minimization- MacroModel Coordinate Scan
- ConfGen Standard- ConfGen- Conformational Search- Conformational Search and Cluster- Premin- Impref- UffminQuantum Mechanics- Jaguar Single Point Energy- Jaguar Minimization- NMR Shielding Constants- Jaguar Charges

Cheminformatics
Fingerprint Based Tools- Fingerprint Generation- Generate Pairwise Matrix- Generate Pairwise Matrix (2 Inputs)- Similarity Matrix (from Molecules)- Dissimilarity Selection (from Matrix)- Build Report for Clustering (from Matrix)- Hierarchical Clustering (from Matrix)
Filters and Mining Tools- Maximum Common Substructure Search- Substructure Search- REOS Filter- Structure Filter
Utilities and Converters- Principal Components- Multi-dimensional Scaling- Combine Fingerprints- Concatenate Bitvectors- Convert Fingerprint to Bitvector- Convert Fingerprint to Table- Convert Matrix to Table- Convert Table to FingerPrint- Convert Table to Matrix- Convert Bitvector to FingerPrint
Modeling- Bayes Classification Model Building

Pharmacophore Modeling- Phase Shape- Phase DB Query- Phase File Query- Phase DB Creation- Phase Hypothesis Identification
Docking and Scoring- Glide Grid Generation- Glide Ligand Docking- Glide Multiple Ligand Docking- XP Visualizer
Post-processing- Prime MM-GBSA- Embrace Minimization- Strain Rescore- Pose Entropy- Pose Filter- Glide Ensemble Merge- Glide Merge-Protein
Glide Sort
ResultsPrediction
Structure- BLAST- Prime Build Homology Model- Prime Side Chain Sampling- Prime Minimization

Schrödinger nodes
Workflows
Protein Preparation- Protein Preparation Wizard- Protein Assignment
Induced-fit docking- IFD and individual steps
Ligand Preparation- LigPrep- Ligprep individual tools (Ionizer,
Desalter, Neutralizer…)- EpikProperty Generation- QikProp- Molecular Descriptors- Calculate properties
Filtering- Ligfilter- Ligparse- Property Filter (Propfilter)
Scripting- Run Maestro Command- Chemistry External Tool 0:1, 1:0, 1:1,
1:2, 2:1 and 2:2 nodes- Python Script 0:1, 1:0, 1:1, 1:2, 2:1 and
2:2 nodes

Desmond- System builder- Molecular Dynamics- Trajectory extract frames and manipulation- Trajectory reader, CMS reader
Reporting- Run Maestro- Run Canvas- View CSV (open xls/ooffice)- Text Viewer
Tools
Combinatorial Libraries- CombiGlide Library Enumeration- CombiGlide Reagent Preparation
Fragments- Fragment Joiner- Fragments from Molecules
Data Manipulation- Compare Ligands- Lookup and Add Columns- Group MAE- Ungroup MAE

Structure Manipulation- Add Hydrogens- Delete Atoms- Split by Structure- MAE Parser- Extract MAE Properties- Delete MAE Properties- Set MAE Properties- Set Molecule Title- Set MAE Index
Utilities- Get PDB
- Align Binding Sites- Protein Structure Alignment- Prime Fix- RMSD- Assign Bond Orders- Unique Title Check- PDB Name
- SD Format Checker- Generate Smarts- Unique Smiles- Entropy Calculation- RRHO Entropy- Boltzmann Population- Volume Overlap Matrix

Readers/Writers- CSV Reader- Molecule Reader- SD, PDB, Mol2 Reader nodes- Sequence Reader- Alignment Reader- Fingerprint Reader- Hypothesis Reader- Glide Grid Reader- Glide Multiple Grid Reader- Variable Based Glide Grid Reader- Molecule Writer- Sequence Writer- Alignment Writer- Hypothesis Writer- Fingerprint Writer
Converters- Molecule-to-MAE- MAE-to-Pdb, to-SD, to-Smiles and to-Mol2- SD-to-Smiles- PoseViewer-to-Complexes- Complexes-to-PoseViewers- String-to-Type- Hartree-to-kcal/mol Converter- kJ-to-kcal Converter

Visual Coherence – Maestro vs. KNIME
Read in
Grid
Read in
Ligands

View
Results

Docking

LigandPreparation
FilteringNodes of general use - Readers and converters• Molecule reader, SD reader... Glide grid reader...
• Converters (Maestro, mae.gz, SD, sd.gz, mol2, PDB, smiles) including Molecule to MAE,
string to type. Canvas converters (Matrix, Fingerprint, Bitvector from and to table). SD
format checker• Pose viewer to complexes and Complexes to PoseViewer

Run maestro command and Run Maestro

Nodes of general use - Structure manipulation• Set MAE properties• Extract MAE properties

Nodes of general use - Structure manipulation• Extract and Set MAE properties• Group and Ungroup, Set MAE index• MAE parser• Split by structure, Delete atoms• Compare ligands• Unique smiles, Unique title check, Ligfilter,
Align binding sites, RMSD,
Volume overlap matrix...

Nodes of general use - Data manipulation and viewers• Look up and add columns• Run Spreadsheet viewer(OpenOffice/Excel)• Table viewer

KNIME Workflows Available for Download

http://www.schrodinger.com/knimeworkflowsOther KNIME Workflows
Cheminformatics

Quantum mechanics

•
•
•
•
•
•

•
•
•
•
•

Cluster by Fingerprint
Database Analysis
Maximum Common Substructure Search (MCS)
Select Diverse Molecules
Similarity Search
Substructure Search

Docking and Post-Processing
•
•
•
•
•
•
•

Docking and Scoring
Ensemble Docking
Loop Over Docking Parameters
Protein Preparation and Glide Grid Generation
Validate Docking Parameters
Virtual Screening
SiteMap

Pharmacophore Modeling•••Phase Hypothesis Identification
Phase Screening
Shape Screening

Molecular Dynamics:•

Desmond Simulation

Molecular Mechanics• Compare Conformational Search Methods• Conformational Search and Post-Processing

Conformational Search and QM Refinement
ESP Charges
Jaguar pKa
Quantum Mechanical Properties
Semi-empirical Optimization

Library Design•

Library Enumeration

Protein Modeling• Induced Fit Docking Protocol• Model Building

Workbench• Group By Use-cases• Group Looper• Unpivot

Real World Examples• Binding Site Shape Clustering• Sitemap and Glide Grid Generation• Vendor Database Preparation

Labs• Glide Grid Writer• Parameter Flow Variable Use-cases• Run Maestro 1:1 Use-cases
General tools• Chemistry External Tool Use-cases• Ensure Molecule Title Uniqueness• Output Column Structure Option Philosophy• Protein Structure Alignment• Python Script Node Use-cases• Run Maestro Command Node Use-cases• Run PyMOL• Split and Align Multimers• Webservice• Workflows in the Current Workspace
http://www.schrodinger.com/knimeworkflows/Schrödinger nodes►• Chemistry tool nodes• Python nodes• Row iterator loop start• Look up and add vs. Joiner node
• Miscellaneous nodes: Compare ligands, Set molecule title

Intermediate
KNIME workbench- GUI- Nodes►►

Schrödinger extensions- Specificities- Schrödinger nodes►►◄ Get started► Advanced functionalities

48

KNIME workbench GUI◄• Preferences• Advanced node functionalities• Errors, warnings and Console information• Flow variables and workflow variables• Metanodes• Memory limit• Tips and tricksPreferences > KNIME• Directory for temporary files (See also Schrödinger preferences ►)• KNIME GUI- disable the node reset, deletion and reconnection
confirmation• KNIME GUI- Console view log level: recommended to change to
INFO. Example of information provided by Schrödinger nodes ►Advanced node functionalities• Hovering over an input connector tells you what the node takes as input (eg Molecules in
Maestro, SMILES or SD format)• Hovering over an output connector reports the number of rows and columns in the output table• Comment a workflow: Node pop-up menu > Node name and description• Data table > change the rendererErrors, warnings and Console information• Popup-menu > View Std output/error• Warning sign above the node statuswhen the node completed with potential
errors• Console information:
INFO

HierarchicalClusteringNodeModel Preparing input file '/tmp/HierarchicalClustering_in_423741.mat'

INFO

HierarchicalClusteringNodeModel Finished preparing file time 0.35 seconds

INFO

HierarchicalClusteringNodeModel 10:42:45 11.17.2009:

Running cmdline[0]='=/usr/local/schro-latest/utilities/canvasHC -im HierarchicalClustering_in_4116794508031023741.mat -ot
HierarchicalClustering_in_4116794508031023741.tree -og HierarchicalClustering_in_4116794508031023741.csv -linkage
schrodinger -n 123'
INFO

HierarchicalClusteringNodeModel Completed time 1.626 seconds

INFO

HierarchicalClusteringNodeModel Preparing output

INFO

HierarchicalClusteringNodeModel Finished preparing output: time 0.06 seconds

INFO

LocalNodeExecutionJob

Hierarchical Clustering (from Matrix) 0:2:50 End execute (2 secs)

Flow variables and workflow variables• The Flow variables are used pass data between nodes on top of the connections.
• In the flow variable tab or the configuration panel for a couple of nodes:• Global variables can also be set: with the Java snippet node ►Or in the Workflow project repository select the workflow and Workflow variables in the pop-up
menu.
See also Schrödinger specificities ► and nodes to edit variables ►Metanodes• To hide the complexity and organize a workflow• Chose the number and type of input/output• The metanodes open up in new tabs

Memory limit• Check the memory limit: Help > About Knime > Installation details > Configuration and search fora line starting with "eclipse.vmargs=-Xmx" (close to the top).
• Increase the memory allocated to KNIME:– $SCHRODINGER\knime -maxHeap 4096m– knime –Xmx4096m (as last option in the command line)– in $SCHRODINGER\knime-v*\bin\*\knime.ini: change -Xmx1024M into 2048M (or higher on
64 bit)• The error message usually contain "Java heap space“ when there is a KNIME is running out ofmemory.
• Preferences > General > Show heap status and use the garbage collector.
• Knime and Schrödinger tools (eg Canvas) don't compete for memory.

Tips and tricks• Copy and paste some nodes to a specific place:
Select, copy the nodes (Ctrl+C), right click where you want to paste thenodes and select Paste in the pop-up menu.
Using Ctrl+V instead the nodes will be pasted a little below the original ones.
• The keyboard shortcuts for items on the menus are listed as usual with themenu item. In File > Preferences > General > Keys you can view all the key
bindings to commands, modify the bindings, and create your own shortcuts.
• All the branches can be run at the same time using the GUI toolbar Executeall executable nodes button. See also Cancel all running nodes.

Known issues• If you can´t save the workflow with a Java heap space error try to disconnect
the last node or run the garbage collector.

KNIME workbench GUI• Report designer• Global variables• Batch execution• Tips and tricks►

KNIME workbench node◄

• KNIME.com Labs nodes• Scripting and run a third party tool
• Java snippet use-cases• Manipulate the table row IDs using the RowID node
• Aggregation using the GroupBy node
• Miscellaneous nodes: Interactive table, Math formula, CDK Sketcher• Plotting facilities• Looping functionalities- Basics• Model building nodes

KNIME.com Labs nodes• Pipeline Pilot Connector (other way around?)• Web Service client, etc
Specific update site: http://labs.knime.org/

Scripting and run a third party tool
• Java snippet ►• Jython and Schrödinger Python nodes ►• Perl scripting• External tool and Schrödinger Chemistry external tool nodes ►• Run Maestro commands ►Java snippet use-cases• Duplicate numeric or string columns• Create a new column from scratch (eg a tag)
• Combine columns (and flow variables) but use the Combiner node forsimple taskseg return "prefix-"+$$FlowVar$$+"_ref_"+$Col1$;• Add a row index (see also Set MAE index)
See the corresponding
workflow example.

Manipulate the table row IDs using the RowID node
• Use data table column values as row IDs and store Row IDs in a column.
Use-cases:– before transposing a data table– Set the labels to be used by the Plotter node

• Ensure row ID uniqueness– eg for Canvas tools before creating a matrix)

Aggregation using the GroupBy nodeSome of the aggregation methods:-

first, last-max, min

-

Mean

-

Sum

-

Concatenate-(unique) count

-

List

-

Set

Miscellaneous nodes• Interactive table: Find & Find Next
equivalent to the Schrödinger Text viewer nodethat have more functionalities• Math formula• CDK Structure sketcher
or Marvin sketch(free of charge from Infocom)

Plotting facilities• Data Views: Plotter, Histogram…
• Mining > Scoring: Enrichment plotter, ROC curve• Advanced capabilities available in KNIME Report designer►

Looping facilities- Basics• Loop start … Loop end• Inject and extract variables• TableRow/Column to and from variables• Prebuilt protocols• Schrödinger node: Row iterator loop start►Model building nodes+ Future Canvas nodes(already some prototypes)

KNIME workbench nodes►• Edit variables and advanced looping functionalities• Hilite functionalities• Database nodes• Miscellaneous useful nodes

Schrödinger extensions specificities• Schrödinger preferences• Start-up script options• Access to the flow variables◄

Schrödinger Preferences• A specific scratch directory can be specified for Schrödinger nodes• Delete temporary files after a node successfully executes
Toggled off to run the calculation through the command line again

Start-up script options
To pass user/machine/OS-specific parameters-maxHeap

Maximum heap size

-maxThreads

Maximum working threads-tempDir

Schrödinger extensions temporary directory-defaultHost

Default host-deleteTempFiles true/false

Delete temporary files on or off.

-ooCmd <value>

Excel / Open Office Spreadsheet commandeg oocalc
or C:\Program Files (x86)\Microsoft Office\Office12\EXCEL.EXE
And more (see knime –h message)

eg 2048 for 2G

Access to the flow variables• Access to the flow variables in the Flow variable tab
including the Chemistry external tools nodes (using %flow_n%)• Variable based Glide grid reader

Schrödinger nodes◄• Chemistry tool nodes• Python nodes• Row iterator loop start• Look up and add vs. Joiner node
• Miscellaneous nodes: Compare ligands, Set molecule title, Get PDB

Chemistry external tool nodes• Input/output types:– Maestro, SD, mol2, Smiles– Double, Integer– String, Text
– Sequence, alignment– FingerPrint, Canvas Matrix– Phase Hypothesis, Glide Grid

Python nodes• Input/output connectors: 0:1,
1:1, 1:2, 2:2• Schrödinger’s APIs
• Possibility to include third
party APIsRow iterator loop start

Look up and add vs. Joiner node
• Take advantage only 1 column, concatenate columns
The Joiner node is the easiest way to concatenate columns when the table havethe same number of rows and same rowIDs.

Miscellaneous nodes• Get PDB: easy way to get one or several structures
use the | symbol as a delimiter for the list of codes• Set molecule title• Compare ligands: the modes are First only, both, either

Schrödinger nodes►• Simple workflow examples• Workflow development support for customers• Automatic protein preparation• Scientifically relevant application of the workflow examples• Interactive work with Knime using the HiLite functionalities• Use a workflow again

Advanced functionalities
KNIME workbench- GUI- Nodes►►

Schrödinger extensions- Advanced workflow examples►◄ Intermediate

KNIME workbench GUI• Report designer• Global variables• Batch execution• Tips and tricks◄

Report designer• From knime.com but free of charge. Included in our distribution• Include To report node(s) in the workflow (can’t be in metanodes) and switch to theReport designer modeReport designer- template modeReport designer- Canvas 2D renderer
The structures can be shown in a report using Canvas 2D renderer using the following procedure:•••

1. In the workflow, add a MAE-to-smiles node and a To report node.
2. In Reporting mode, in the Layout tab, add a table to the report (drag and drop from the Data
set view).
3. Insert in the "[smiles]" cell (Table- detail row) an Image widget from the Report Items list.

•

4. Configure the widget (using "Edit" on the widget), select "Dynamic image", and press "SelectImage Data..." to select the source column (which should be the Smiles column). Delete "[smiles]"if you want just the image and no SMILES. You may want to alter the size of the cell by dragging
the border vertically and horizontally if necessary.

•

5. Change the size of the image to something like 300x300, which is done by editing the Data setview (right click -> Edit -> Parameters), and changing (or creating new Parameters typed as
integer if they don't exist yet) the knime-image-height and knime-image-width parameters.

•

6. Check the view in the Preview tab

Global variables• In the Workflow project list, right-click on the workflow, under Workflow variables

Batch execution• $SCHRODINGER/knime -batch –reset –nosplash -nosave-workflowFile=<path>/<wkf>.zip or -workflowDir=<path>/<workspace>/<wkf>• Alter some settings -option=nodeNumber,valueName,value,type-option=7,filename,"/tmp/new-molprops.csv",String(int, double or String)

Find the node number in the configuration panel header (add the metanode numbers)
eg 123/456/78 for the node 78 in the metanode 456 in the metanode 123
Find the option name in the workspace directory: <workflow>/node_name(#7)/node.xml<config key="DataURL"><entry key="array-size" type="xint" value="1" /><entry key="0" type="xstring" value="/C:/serotonin_unique.sdf" />-option=2,DataURL\0,"file:/tmp/new-input.mae",String
When the input is an array• Pass some variables: -workflow.variable=name,value,type (int, double or String)• Workflows can be run from Maestro using a simple Python script wrappereg:Tips and tricks• Rearrange the panels• Workflow Meta-Infos• Try to open a workflow modified with a newer version of KNIME alter the 2following lines of the file<workspace>/<workflow>/workflow.knime:<entry key="created_by" type="xstring" value="2.0.3.0021120"/><entry key="version" type="xstring" value="2.0.0"/>

KNIME workbench nodes◄• Edit variables and advanced looping functionalities• HiLite functionalities• Database nodes• Miscellaneous useful nodes

Edit variables and advanced looping functionalities• Extract variable (data) and Inject variable (data)• TableRow to Variable (use the first row), Variable toTableRow and Variable to TableColumn

Hilite functionalities• HiLite filter and HiLite collector nodes• Color, Size and Shape Manager/Appender nodes

Database nodes• See simple examples (not on the Workflow page yet)Time series support• See simple examples (not on the Workflow page yet)

Miscellaneous nodes: Cell splitter, Numeric binner• Reference row filter, Reference column filter, Nominal value row filter• Missing values• Create collection column and Split collection• Text manipulation: String replacer, Case converter, Cell splitter• Row sampling, Partitioning, Shuffle• Numeric binnerKNIME workflow examples◄• KNIME workflow page
• Workflow development support for customers• Workflow example presentation

KNIME workflow page - http:/www.schrodinger.com/knimeworkflows/
Cheminformatics• Substructure Search• Clustering, diversity selection, similarity search• Database analysis• Maximum Common Substructure
Docking and post-processing• Protein preparation and Glide grid generation• Docking and scoring, Virtual screening, Ensemble docking, Induced Fit
Docking• Loop over docking parameters• Validate docking parameters
Pharmacophore modeling• Phase Shape screening•

Phase hypothesis identification•

Phase database screening

Molecular Mechanics•

Compare conformational search methods

Quantum mechanics•

Conformational search and QM optimization
Using the Report designer

Homology modeling• Model building and refinement
Library design• Library enumeration
including a Run Maestro 1:1 prototype
Real World Examples• Vendor database preparation
General tools• Python script node use-cases
including a Run PyMOL prototype• Chemistry external tool node use-cases• Run maestro command node use-cases• Output column structure option philosophy
KNIME workbench• Workflows in the current workspace
KNIME workbench- looper• Group Looper
Simplest, most exciting, new and improved workflows

Workflow development support for customers
Combine or expand the workflow examples• Hierarchical clustering and diverse compounds from each cluster
Waiting for new nodes to be developed• CombiGlide library enumeration, MacroModel coordinate scan (now available)• PCA on per residue interactions(Chemistry external tool node)• Distance measurement in protein and run script in Maestro, descriptor calculation, create protein mutants(Python script node)
Specific workflows• Various MacroModel protocols using the Python node for accessing advanced functionalities (eg contraints)• Prime MM-GB/SA on a set of complexes (ligand detection, flexible residues)• Simplifying compound docking with KNIME, Dr. Robert Happel, Boehringer Ingelheim, Vienna
http://www.schrodinger.com/seminarprior/19/26/• Cris Guimaraes MM-GB/SA paper reproduction and improvements
http://www.schrodinger.com/Download.php?type=seminarentry&type2=slides&ident=105• Protein preparation protocol

Real World Case Study: Binding Site Clustering and Ensemble Docking

Real life applications...

Workflow example presentation
Feel free to request this other presentation including:• Simple examples• More advanced examples from the Workflow page
• Scientifically relevant applications

Schrödinger KNIME Extensions
KNIME Extensions Product Manager:

Jean-Christophe Mozziconacci(jcmozzic@schrodinger.com)

Vice President of Technology:
Main Developer:

Volker Eyrich

Ravikiran Kuppuraj
and the PyDev development team

QA:

Simon Foucher

Workflow examples:

Tanvi Bhola

Technical Support:

Katalin Phimister, Pavel Golubkov

Marketing:

Jarred Yacob