Knowledge-based Design of Target-focused Libraries Using Protein-ligand Interaction Constraints.
From: Computational Drug Design Group, Biogen Idec, Inc., Cambridge, Massachusetts 02142, USA.
Journal of medicinal chemistry
- Publish Date: Jan 2006
- ISSN: 0022-2623
- Volume: 49
- Issue: 2
- Pages: 490-500
- Medium: Print
- Language: English
- Citation (JAMA): Deng Zhan, Chuaqui Claudio, Singh Juswinder, et al. Knowledge-based Design of Target-focused Libraries Using Protein-ligand Interaction Constraints.. J. Med. Chem. Jan 2006;49:490-500
Abstract
Here we present a new strategy for designing and filtering potentially massive combinatorial libraries using structural information of a binding site. We have developed a variation of the structural interaction fingerprint (SIFt) named r-SIFt, which incorporates the binding interactions of variable fragments in a combinatorial library. This method takes into account the 3D structure of the active site of the target molecule and translates desirable ligand-target binding interactions into library filtering constraints. We show using the MAP kinase p38 as a test case that we can efficiently analyze and classify compounds on the basis of their abilities to interact with the target in the desired binding mode. On the basis of these classifications, decision tree models were generated using the molecular descriptors of the compounds as predictor variables. Our results suggest that r-SIFt coupled with the classification models should be a valuable tool for structure-based focusing of combinatorial chemical libraries.
Mesh Headings (Keywords): Binding Sites, Combinatorial Chemistry Techniques, Databases, Factual, Knowledge Bases, Ligands, Models, Molecular, Molecular Structure, Protein Binding, Proteins, Quantitative Structure-Activity Relationship
Check for Full Text / PubMed Unique Identifier (PMID): 16420036
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.