Chemometrical Classification of Ephrin Ligands and Eph Kinases Using GRID/CPCA Approach
| Title: | Chemometrical Classification of Ephrin Ligands and Eph Kinases Using GRID/CPCA Approach |
|---|---|
| Authors: | Myshkin, Eugene, Wang, Bingcheng |
| Source: | Journal of Chemical Information and Modeling; May 2003, Vol. 43 Issue: 3 p1004-1010, 7p |
| Abstract: | Eph receptor tyrosine kinases are divided on two subfamilies based on their affinity for ephrin ligands and play a crucial role in the intercellular processes such as angiogenesis, neurogenesis, and carcinogenesis. As such, Eph kinases represent potential targets for drug design, which requires the knowledge of structural features responsible for their specific interactions. To overcome the existing gap between available sequence and structure information we have built 3D models of eight ephrins and 13 Eph kinase ligand-binding domains using homology modeling techniques. The interaction energies for several molecular probes with binding sites of these models were calculated using GRID and subjected to chemometrical classification based on consensus principal component analysis (CPCA). Despite inherent limitations of the homology models, CPCA was able to successfully distinguish between ephrins and Eph kinases, between Eph kinase subfamilies, and between ephrin subfamilies. As a result we have identified several amino acids that may account for selectivity in ephrin−Eph kinase interactions. In general, although the difference in charge between ephrin and Eph kinase binding domains creates an attractive long-range electrostatic force, the hydrophobic and steric interactions are highly important for the short-range interactions between two proteins. The chemometrical analysis also provides the pharmacophore model, which could be used for virtual screening and de novo ligand design. |
| Database: | Supplemental Index |
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| Items | – Name: Title Label: Title Group: Ti Data: Chemometrical Classification of Ephrin Ligands and Eph Kinases Using GRID/CPCA Approach – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Myshkin%2C+Eugene%22">Myshkin, Eugene</searchLink><br /><searchLink fieldCode="AR" term="%22Wang%2C+Bingcheng%22">Wang, Bingcheng</searchLink> – Name: TitleSource Label: Source Group: Src Data: Journal of Chemical Information and Modeling; May 2003, Vol. 43 Issue: 3 p1004-1010, 7p – Name: Abstract Label: Abstract Group: Ab Data: Eph receptor tyrosine kinases are divided on two subfamilies based on their affinity for ephrin ligands and play a crucial role in the intercellular processes such as angiogenesis, neurogenesis, and carcinogenesis. As such, Eph kinases represent potential targets for drug design, which requires the knowledge of structural features responsible for their specific interactions. To overcome the existing gap between available sequence and structure information we have built 3D models of eight ephrins and 13 Eph kinase ligand-binding domains using homology modeling techniques. The interaction energies for several molecular probes with binding sites of these models were calculated using GRID and subjected to chemometrical classification based on consensus principal component analysis (CPCA). Despite inherent limitations of the homology models, CPCA was able to successfully distinguish between ephrins and Eph kinases, between Eph kinase subfamilies, and between ephrin subfamilies. As a result we have identified several amino acids that may account for selectivity in ephrin−Eph kinase interactions. In general, although the difference in charge between ephrin and Eph kinase binding domains creates an attractive long-range electrostatic force, the hydrophobic and steric interactions are highly important for the short-range interactions between two proteins. The chemometrical analysis also provides the pharmacophore model, which could be used for virtual screening and de novo ligand design. |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1021/ci0256586 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 1004 Titles: – TitleFull: Chemometrical Classification of Ephrin Ligands and Eph Kinases Using GRID/CPCA Approach Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Myshkin, Eugene – PersonEntity: Name: NameFull: Wang, Bingcheng IsPartOfRelationships: – BibEntity: Dates: – D: 27 M: 05 Text: May 2003 Type: published Y: 2003 Identifiers: – Type: issn-print Value: 15499596 – Type: issn-print Value: 1549960X Numbering: – Type: volume Value: 43 – Type: issue Value: 3 Titles: – TitleFull: Journal of Chemical Information and Modeling Type: main |
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