Cheminformatics tools, workflows and pipelines for substructure search, virtual screening and data analysis
The following six steps are required to try out the fast substructure search in combinatorial library spaces. In this example we create the necessary datastructures from a provided input file containing a toy combinatorial library space consisting of 30k structures.
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Download and build with maven, i.e. just use "mvn package", or alternatively import into Intellij and execute the maven task "mvn package"
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A successful build should create the .jar file openchemlib-hyperspace-cli/target/openchemlib-hyperspace-cli.jar , check that it exists
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Switch to the example subfolder and copy the openchemlib-hyperspace-cli.jar file in there
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Create hyperspace data file from example space file "idorsia_toy_space_a.txt". This is a virtual library that we used for validation of the algorithms. It contains a few synthon reactions and in total around 30k structures, i.e. it is easily possible to compare search results of Hyperspace against normal enumerated search.
To do this use the following command:
java -jar openchemlib-hyperspace-cli.jar CREATESPACE idorsia_toy_space_a.txt test FragFp 2
Explanation of the parameters after CREATESPACE: (1) input file name (2) name of the space that you want to create (determines the output file name) (3) descriptor name (must be FragFp for substructure search), (4) number of threads for space creation.
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Start the GUI for interactive search in our toy space
java -jar openchemlib-hyperspace-cli.jar GUI hyperspace_test_config.json
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Try out some queries using OpenChemLib query features, e.g. "foA@@@DjU_YVgKNBBJ@@@@vpA``". Please check the section Hyperspace GUI Manual below for instructions on how to use the software.
You can now run substructure searches against the 30k structures.
Maven is used as build tool. The project is organized as a Maven project "openchemlib-hyperspace" containing a number of different submodules. The parent project has a fixed version "DEV-snapshot" / "dev". The actual version of the different submodules is specified via the propery ${revision}.
hyperspace-core Provides datastructures and algorithms to represent and search in combinatorial libraries (aka. synthon spaces).
hyperspace-core-gui Provides GUI elements and server/client tools that enable search / virtual screening.
hyperspace-tools Contains tools to parse combinatorial libraries in synthon representation and create the hyperspace data files.
hyperspace-sar Coming soon.
Provides algorithms and datastructures to represent combinatorial libraries in synthon representation. Provides algorithms for fast fingerprint filtering, enabling fast substructure searching in enumerated libraries. Provides full algorithm for substructure searching in enumerated libraries. Provides implementations of similarity search algorithms for combinatorial libraries.
Most important classes: com.idorsia.research.chem.hyperspace.SynthonSpace Serializable class that represents a combinatorial library in synthon representation. Provides methods for fast substructure search.
com.idorisa.research.chem.hyperspace.SynthonSimilaritySpace3 Serializable class that extends a SynthonSpace by methods for similarity searching.
Provides a basic extendable GUI to provide search functionality. The GUI can be extended by implementing "search providers" that provide GUI and logic for searching. Contains default implementations for hyperspace similarity and substructure search. The GUI also provides tools to help with the implementation of server / client based searching. It further contains a substructure search service that provides substructure search capability for the datawarrior hyperspace substructure plugin.
Example launch of server
java -Xmx16G -jar <path_to_hs_server_jar> com.idorsia.research.chem.hyperspace.gui.HyperspaceServer -t <num_threads_per_query> -s <max_num_simultaneous_queries> -p <port> --init <path_to_json_config_file>
java -Xmx16G -jar <path_to_hs_server_jar> com.idorsia.research.chem.hyperspace.gui.HyperspaceServer -t 12 -s 4 -p 8090 --init server_config.json
The file server_config.json just contains the different available search services. A search service has a specific specific search service name, the serviceProvider must be specified and the configuration for the service provider must be provided.
{
"ServiceProviders":[
{
"ServiceName":"REAL Space SSS",
"ServiceProvider":"HyperspaceSSS",
"Config":{
"SpaceName":"REAL Space",
"File":"/home/liphath1/hyperspace_base_2/data_hyperspace/REAL_Space_latest_FragFp.data",
"MaxNumberOfThreads":-1
}
},
{
"ServiceName":"Idorsia VCS 3.2 (2S) SSS",
"ServiceProvider":"HyperspaceSSS",
"Config":{
"SpaceName":"IVCS 3 (2S)",
"File":"/home/liphath1/hyperspace_base_2/data_hyperspace/ivcs3_2s_FragFp.data",
"MaxNumberOfThreads":-1
}
},
{
"ServiceName":"REAL Space SSS DWService",
"ServiceProvider":"HyperspaceSSSForDW",
"Config":{
"SpaceName":"REAL Space",
"File":"/home/liphath1/hyperspace_base_2/data_hyperspace/REAL_Space_latest_FragFp.data"
}
}
]
}
Example launch of GUI:
java -Xmx16G -jar <path_to_hyperspace_server_jar> com.idorsia.research.chem.hyperspace.gui.HyperspaceSearchGUI <path_to_json_config_file>
The structure of the config file for the GUI is the same as for the server, i.e. it is a list of service provider configurations. There are remote service providers available, that allow to send queries to a hyperspace server. The "SearchServiceName" has to agree with the configured service name of the service provider running on the server.
Example Standard (local) configuration
Exactly the same as the configuration of the server (however, only search providers that provide a GUI can be used, but most search providers do).
Example Remote configuration
{
"ServiceProviders":[
{
"ServiceName":"REAL Space SSS",
"ServiceProvider":"HyperspaceSSSRemote",
"Config":{
"Server":"hyperspaceserver",
"Port":"8090",
"SearchServiceName":"REAL Space SSS",
"GUIServiceName":"REAL Space SSS"
}
},
{
"ServiceName":"IVCS3 2S SSS",
"ServiceProvider":"HyperspaceSSSRemote",
"Config":{
"Server":"hyperspaceserver",
"Port":"8090",
"SearchServiceName":"Idorsia VCS 3.2 (2S) SSS",
"GUIServiceName":"IVCS 3 (2s) SSS"
}
},
{
"ServiceName":"REAL Space Sim",
"ServiceProvider":"HyperspaceSimilarityRemote",
"Config":{
"Server":"hyperspaceserver",
"Port":"8090",
"SearchServiceName":"REAL Space Similarity",
"GUIServiceName":"REAL Space Similarity"
}
},
{
"ServiceName":"IVCS3 2S Sim",
"ServiceProvider":"HyperspaceSimilarityRemote",
"Config":{
"Server":"hyperspaceserver",
"Port":"8090",
"SearchServiceName":"Idorsia VCS 3.2 (2S) Similarity",
"GUIServiceName":"IVCS 3 (2s) Similarity"
}
}
]
}
Provides tools to create the hyperspace data files that can be loaded by the search providers of the tools in hyperspace-server.
Example for parsing / creating hyperspace data files for substructure search:
java -Xmx16G com.idorsia.research.chem.hyperspace.io.SynthonSpaceParser2 /home/liphath1/hyperspace_base_2/data/REAL_Space_latest/2021-02_REAL_synthons_SMALL.txt <name_of_space_file> FragFp <number_of_threads>
This creates a synthon space with "FragFp" descriptors. This is the descriptor / space that is necessary for the substructure search services.
The input file format is a tsv (tab separated values) file with the following format: first line is header line (and is not parsed) all other lines are:
- synthon in smiles, 2. a synthon id, 3. an integer specifying the synthon set of the synthon reaction, 4. the synthon reaction
i.e. the following file would create two synthon reactions, each with two synthon sets (synthon reaction r1 has 2x2 synthons, synthon reaction r2 has 1x3 synthons to assemble). Of course the synthons must have matching connectors (i.e. matching transuranium elements (atomic mass 92-99), that uniquely identify each possible connection point). All synthons of a synthon set of a reaction must have the same connectors (i.e. a single U, or Np and Pu, etc.). The correctness of synthons is checked during the creation of the datastructures and in case of problems, the software will output error messages for the problematic synthons / synthon reactions.
smiles synthon synton# reaction_id
smiles1 r1_1_s1 1 r1
smiles2 r1_1_s2 1 r1
smiles3 r1_2_s1 2 r1
smiles4 r1_2_s2 2 r1
smiles5 r2_1_s1 1 r2
smiles6 r2_2_s1 2 r2
smiles7 r2_2_s2 2 r2
smiles8 r2_2_s3 2 r2
- Thomas Liphardt