Linked Life Data

9986717

Source:http://linkedlifedata.com/resource/pubmed/id/9986717

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-3-16
pubmed:abstractText
Three-dimensional quantitative structure-activity relationship (3D QSAR) methods were applied using a training set of 72 inhibitors of the benzamidine type with respect to their binding affinities (Ki values) toward thrombin, trypsin, and factor Xa to yield statistically reliable models of good predictive power. Two methods were compared: the widely used comparative molecular field analysis (CoMFA) and the recently reported CoMSIA approach (comparative molecular similarity indices analysis). CoMSIA produced significantly better results for all correlations. Furthermore, in contrast to CoMFA, CoMSIA is not sensitive to changes in orientation of the superimposed molecules in the lattice. The correlation results obtained by CoMSIA were graphically interpreted in terms of field contribution maps allowing physicochemical properties relevant for binding to be easily mapped back onto molecular structures. The advantage of this feature is demonstrated using the maps to design new molecules. Finally, the CoMSIA method was applied to elucidate structural features among ligands which are responsible for affinity differences toward thrombin and trypsin. These selectivity-determining features were interpreted graphically in terms of spatial regions responsible for affinity discrimination. Such indicators are highly informative for the lead optimization process with respect to selectivity enhancement.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
458-77
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Three-dimensional quantitative structure-activity relationship analyses using comparative molecular field analysis and comparative molecular similarity indices analysis to elucidate selectivity differences of inhibitors binding to trypsin, thrombin, and factor Xa.
pubmed:affiliation
Department of Pharmaceutical Chemistry, University of Marburg, Marbacher Weg 6, D-35032 Marburg, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't