Linked Life Data

20527883

Source:http://linkedlifedata.com/resource/pubmed/id/20527883

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-6-28
pubmed:abstractText
In the early stage of drug discovery programs, when the structure of a complex involving a target and a small molecule is available, structure-based virtual ligand screening methods are generally preferred. However, ligand-based strategies like shape-similarity search methods can also be applied. Shape-similarity search methods consist in exploring a pseudo-binding-site derived from the known small molecule used as a reference. Several of these methods use conformational sampling algorithms which are also shared by corresponding docking methods: for example Surflex-dock/Surflex-sim, FlexX/FlexS, ICM, and OMEGA-FRED/OMEGA-ROCS. Using 11 systems issued from the challenging "own" subsets of the Directory of Useful Decoys (DUD-own), we evaluated and compared the performance of the above-cited programs in terms of molecular alignment accuracy, enrichment in active compounds, and enrichment in different chemotypes (scaffold-hopping). Since molecular alignment is a crucial aspect of performance for the different methods, we have assessed its impact on enrichment. We have also illustrated the paradox of retrieving active compounds with good scores even if they are inaccurately positioned. Finally, we have highlighted possible positive aspects of using shape-based approaches in drug-discovery protocols when the structure of the target in complex with a small molecule is known.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1549-960X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
992-1004
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Comparative evaluation of 3D virtual ligand screening methods: impact of the molecular alignment on enrichment.
pubmed:affiliation
Unite de Bioinformatique Structurale, Institut Pasteur, 26 rue du Dr Roux, 75015 Paris, France.
pubmed:publicationType
Journal Article, Comparative Study