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  • Poster presentation
  • Open Access

Multi-parameter scoring functions for ligand- and structure-based de novo design

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Journal of Cheminformatics20102 (Suppl 1) :P31

  • Published:


  • Drug Discovery
  • Related Property
  • Polar Surface
  • Score Component
  • Polar Surface Area

Successful drug discovery often requires optimization against a set of biological and physical properties. We describe de novo design studies that demonstrate successful scaffold hops between known classes of ligands for p38 MAP kinases using ligand-based and structure-based multi-parameter scoring functions coupled to the molecular invention engine Muse.

The ligand-based scoring function includes pharmacophoric and steric tuplets and structural (fingerprint based) similarity. In addition various selectivity or ADME related properties (e.g. Lipinski properties, polar surface area, activity at off-targets, etc.). can be taken into account to guide the evolution of structures meeting multiple design criteria.

The structure-based scoring function uses Surflex-Dock to pose and score invented structures inside the target's active site. In addition, a number of simple molecular properties (e.g. clogP, Lipinski properties, etc.) are used as score components to focus the design on medicinally relevant chemistries. With the ability of Surflex-Dock to start the docking process with a single or multiple placed fragments, this scoring function can be applied in fragment based drug discovery to optimize attachments onto a pre-placed substructure.

Authors’ Affiliations

Tripos International, Martin-Kollar-Str. 17, 81829 München, Germany
St. Louis, USA
Shanghai, PR China


© Fabian et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.