Linked Life Data

18786843

Source:http://linkedlifedata.com/resource/pubmed/id/18786843

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-11-18
pubmed:abstractText
Pharmacophore modeling, including ligand- and structure-based approaches, has become an important tool in drug discovery. However, the ligand-based method often strongly depends on the training set selection, and the structure-based pharmacophore model is usually created based on apo structures or a single protein-ligand complex, which might miss some important information. In this study, multicomplex-based method has been suggested to generate a comprehensive pharmacophore map of cyclin-dependent kinase 2 (CDK2) based on a collection of 124 crystal structures of human CDK2-inhibitor complex. Our multicomplex-based comprehensive pharmacophore map contains almost all the chemical features important for CDK2-inhibitor interactions. A comparison with previously reported ligand-based pharmacophores has revealed that the ligand-based models are just a subset of our comprehensive map. Furthermore, one most-frequent-feature pharmacophore model consisting of the most frequent pharmacophore features was constructed based on the statistical frequency information provided by the comprehensive map. Validations to the most-frequent-feature model show that it can not only successfully discriminate between known CDK2 inhibitors and the molecules of focused inactive dataset, but also is capable of correctly predicting the activities of a wide variety of CDK2 inhibitors in an external active dataset. Obviously, this investigation provides some new ideas about how to develop a multicomplex-based pharmacophore model that can be used in virtual screening to discover novel potential lead compounds.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1873-4243
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
430-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Towards more accurate pharmacophore modeling: Multicomplex-based comprehensive pharmacophore map and most-frequent-feature pharmacophore model of CDK2.
pubmed:affiliation
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't