Hyperspace Search: Precisely Configurable Hit Expansion in 2D



Overview
Example Result
Query Features
Hyperspace Explorer
Access Plans and Pricing
References

Overview


Hyperspace Search is a blazingly-fast 2D virtual screening tool for precise substructure and structure similarity search designed to address the computational complexities posed by ultra-large combinatorial spaces. The following key performance areas are addressed to maximize the virtual screening experience for you:

- Blazingly Fast Discovery: Perform precise substructure and structure similarity searches with a median search time of just 2 seconds per space. The boxplot below highlights our performance across more than 6,500 recent searches.

- Unmatched Chemical Diversity at Scale: Gain immediate access to over 60 trillion diverse, make-on-demand compounds from 9 globally trusted vendors. As illustrated in the color UMAP here, our collection is curated for deep structural diversity to maximize the success of your lead discovery.

- Complete Query Configurability: Precisely define atom types, bond types, ring sizes, exclude groups, bridge bonds, and other substitution patterns. These features allow you to assert total control over your substructure and structure similarity search to find exactly what your project demands, and to a limited extend such queries even allow for some scaffold hopping.

- Flexible Access & Integration: Harness the full power of the Alipheron collection via our intuituive GUI or automate your discovery using our REST API. Our interface ensures a seamless experience from your workspace, regardless of how you search or where you are located.

- 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 defined aboved to fine-tune your search. In similarity mode, adjust the threshold slider for a comprehensive search of entire molecules.


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.

Query Features



Query features are a powerful and practical concept boosting substructure and similarity searching in cheminformatics. It uses a chemist's intuition to explain how to build substructure queries that include detailed structural information. This can cover everything from stereo centers and exclude groups to variable ring sizes and atomic chain configurations, and more. The concept is implemented in DataWarrior as well.

More generally, various aspects of a compound such as chain lengths, exclude groups, and logical operators of the query are defined in the structure editor in DataWarrior and can be parameterized. Let us look at one more example in a bit more detail. In the structure editor below, you see a query structure configuration to illustrate how to define variable atom bridges, variable ring systems with excluded atoms and stereo centers, and lastly atomic chain composition.


Configurations to yield the parameterization of the query structure depicted in the structure editor above can be accomplished in the control panels depicted below.



Hyperspace Explorer


Alipheron Hyperspace Explorer is ideal for medicinal chemists and computational scientists who want to go beyond single-molecule queries. It enables both forward exploration of combinatorial spaces through pharmacophore-guided query expansion and reverse analysis of screening results, such as clustering thousands of hits from DEL or high-throughput campaigns into meaningful pharmacophore families for downstream prioritization.


Main Features


  • Advanced Query Expansion: Creation of topological pharmacophore patterns enabling efficient identification of structurally and pharmacologically relevant derivatives within vast chemical spaces.
  • Inversion: Clustering of thousands of high-throughput hits according to shared pharmacophore patterns.
  • DEL Screening Application: Unique functionality for organizing DNA-encoded library results.

Hyperspace Explorer is an extension of Hyperspace Search, designed to unlock new dimensions of chemical space exploration. By transforming query molecules into topological pharmacophore patterns, it enables the discovery of structurally and pharmacologically relevant derivatives within ultra-large combinatorial spaces. In addition, its inversion allows clustering of thousands of high-throughput hits by shared pharmacophore patterns, and is therefore uniquely suited for organizing DNA-encoded library (DEL) screening results.


Access Plans and Pricing


For details on subscription options, please see plans.

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