Volume 3 Supplement 1

4th German Conference on Chemoinformatics: 22. CIC-Workshop

Open Access

Glide XP fragment docking and structurebased pharmacophores

  • W Sherman1 and
  • R Friesner2
Chemistry Central Journal20093(Suppl 1):P45

https://doi.org/10.1186/1752-153X-3-S1-P45

Published: 05 June 2009

In recent years, fragment-based drug design has become increasingly popular. Common computational approaches include building fragments up sequentially, or linking disparate fragments. However, the former approach can restrict the exploration of chemical space and may produce ligands that are not sufficiently drug-like, whereas the latter approach may result in difficulties when linking together the individual fragments.

Here, we describe a third approach that avoids these problems with the use of fragment-derived pharmacophore hypotheses. In our computational workflow a pharmacophore hypothesis is created using fragments docked and ranked by Glide XP, and virtual databases are screened against this hypothesis using Phase [1]. In an initial validation study on P38 Map Kinase, known active compounds were successfully retrieved and good enrichment factors were obtained.

Authors’ Affiliations

(1)
Schrödinger Inc
(2)
Department of Chemistry, Columbia University

References

  1. Dixon SL: J Comput Aided Mol Des. 2006, 20: 647-671. 10.1007/s10822-006-9087-6.View ArticleGoogle Scholar

Copyright

© Sherman and Friesner; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.