Enrichment of ligands for the serotonin receptor using the shape signatures approach

Karthigeyan Nagarajan, Randy Zauhar, William J. Welsh

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Shape Signatures, a new 3-dimensional molecular comparison method, has been adapted to rank ligands of the serotonin receptors. A set of 825 agonists and 400 antagonists together with approximately 10 000 randomly chosen compounds from the NCI database were used in this study. Both ID and 2D Shape Signature databases were created, and enrichment studies were carried out. Results from these studies reveal that the ID Shape Signature approach is highly efficient in separating agonists from a mixture of molecules which includes compounds randomly selected from the NCI database taken as inactives. It is also equally effective at separating agonists and antagonists from a pool of active ligands for the serotonin receptor. Parallel enrichment studies using 2D shape signatures showed high selectivity with more restricted coverage due to the high specificity of 2D signatures. The influence of conformational variation of the shape signature on enrichment was explored by docking a subset of ligands into the crystal structure of serotonin N-acetyltransferase. Enrichment studies on the resulting "docked" conformations produced only slightly improved results compared with the CORINA-generated conformations.

Original languageEnglish (US)
Pages (from-to)49-57
Number of pages9
JournalJournal of Chemical Information and Modeling
Volume45
Issue number1
DOIs
StatePublished - Jan 2005

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences

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