Hyperspace: Blazingly-Fast Substructure and Structure Similarity Search

Overview
Example Result
Real-Time Demonstration
Getting Started
Access and Pricing
References

Overview


Hyperspace is Alipheron's technology to search ultra-large combinatorial spaces for molecules that have a given substructure or that have a similar structure to a given query molecule. Substructure searches may contain atom or bond based query features as requiring an atom to be aromatic or a bond to be part of a five-membered ring. In particular you can add exclude groups to define substituents that are not allowed at certain position. Or you may connect two ring systems by a chain of bonds with a defined allowed range for the number of bonds in between. To a limited extend such queries allow even scaffold hopping. Typically, searches with Hyperspace return thousands of matching molecules within less than a minute of search time.


Example Result


For illustration purposes, suppose that the activity of Iptacopan is essentially triggered by the two substructures marked in red on the left-hand side. The corresponding query structure, i.e., a potential input for Hyperspace is depicted on the right-hand side. Note, for instance, the dashed 'bridge bond' marked with '3:5', which defines a connecting chain with three, four, or five atoms. The yellowed-out nitrogen and oxygen in the substructure represent that further substitution at these position is prohibited.


Real-Time Demonstration


There are two search modes: 'Superstructures of' to find molecules containing the specified substructure, or 'Similar structures to' to search based on chemical similarity. In substructure mode, use advanced query features such as exclude groups or bond bridges to fine-tune your search. In similarity mode, adjust the threshold slider for a comprehensive search of entire molecules, such as drugs.




Getting Started


The Hyperspace plugin facilitates ultra-fast substructure or similarity searches and gives you immediate access to trillions of readily synthesizable molecules in the Alipheron ULCL Collection which is composed of ultra-large combinatorial libraries by our well-trusted partners.

  1. Download and install DataWarrior.
  2. Start DataWarrior and allow automatic update in Help>Update Mode.
  3. Install the Hyperspace plugin: Select Help>Trusted Plugins

  4. Restart DataWarrior; a new menu Alipheron has been created. Select Hyperspace Search....

  5. Register with your name and email to receive a passcode on your given e-mail address.

  6. Enter the pass code in DataWarrior's dialog and that's it! You can start searching! Under the hood you have received a token connected to your e-mail address that is stored locally on your computer and used in the future as access key for Hyperspace searches.

  7. Now select the Library to be searched and select, whether to search for superstructures or structures being similar to your query. Then double-click the Query Structure field to open the structure editor. Here you may draw or paste a (sub)structure or even a chemical name. If you have selected superstructure mode, then you can associate atoms and bonds with query features (select the lasso tool and double click atoms/bonds). You may also attach exclude groups to particular atoms, which are groups that are not allowed at this position.

  8. Click OK and, within seconds you'll receive a comprehensive list of matching structures.


Access and Pricing


Substructure and similarity searches are free up to a certain daily limit and with a limited number of results. The token concept is as follows:

  • Your token starts at 25 credits and is replenished every 24 hours.
  • A successful similarity or substructure search deducts 5 credits from your token.
  • Free similarity or substructure searches are limited to 999 result rows.

Searches with purchased tokens cost 10 credits, but return up to 10'000 rows. Hyperspace can be installed as an in-house solution that offers private searches on the Alipheron ULCL Collection as well as on your company's custom-built in-house spaces. You can purchase more credits for your token using Paypal or a credit card, or inquire about licensing options directly with us at contact@alipheron.com.


References


  • Fully Automated Creation of Virtual Chemical Fragment Spaces Using the Open-Source Library OpenChemLib; J Wahl, T Sander; Journal of Chemical Information and Modeling, 2022, 62 (9), 2202–2211; https://doi.org/10.1021/acs.jcim.1c01041

  • Fast Substructure Search in Combinatorial Library Spaces; T Liphardt, T Sander; Journal of Chemical Information and Modeling, 2023, 63 (16), 5133–5141; https://doi.org/10.1021/acs.jcim.3c00290