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EAI-TupletScore, a pharmacophore and shape driven ligand-based de-novo design algorithm

We describe a ligand-based de-novo design algorithm EAI-TupletScore and studies that demonstrate its ability to successfully generate lead hops between different classes of active ligands from the DUD dataset [1]. EAI-TupletScore uses the de-novo design engine EA-Inventor with a Pareto-Borda [2][3] scoring method that employs pharmacophore and steric tuplets [4], as well as UNITY fingerprint similarities to a set of lead compounds to design novel ligands that maximize pharmacophore and shape similarity, while maintaining a certain level of structural dissimilarity, to these lead compounds. EAI-TupletScore, can be used to design novel ligand scaffolds (lead generation or lead hopping) or to optimize attachments on a fixed scaffold (lead optimization).

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Correspondence to KM Smith.

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Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Shape Similarity
  • Design Algorithm
  • Lead Compound
  • Active Ligand
  • Lead Optimization