Volume 2 Supplement 1

5th German Conference on Cheminformatics: 23. CIC-Workshop

Open Access

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

  • Fabian Bös1,
  • KM Smith2 and
  • Q Liu3
Journal of Cheminformatics20102(Suppl 1):P31


Published: 04 May 2010

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, 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.