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Combining selectivity and affinity predictions using an integrated Support Vector Machine (SVM) approach: An alternative tool to discriminate between the human adenosine A(2A) and A(3) receptor pyrazolo-triazolo-pyrimidine antagonists binding sites.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2009 Jul 15; Vol. 17 (14), pp. 5259-74. Date of Electronic Publication: 2009 May 21. - Publication Year :
- 2009
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Abstract
- G Protein-coupled receptors (GPCRs) selectivity is an important aspect of drug discovery process, and distinguishing between related receptor subtypes is often the key to therapeutic success. Nowadays, very few valuable computational tools are available for the prediction of receptor subtypes selectivity. In the present study, we present an alternative application of the Support Vector Machine (SVM) and Support Vector Regression (SVR) methodologies to simultaneously describe both A(2A)R versus A(3)R subtypes selectivity profile and the corresponding receptor binding affinities. We have implemented an integrated application of SVM-SVR approach, based on the use of our recently reported autocorrelated molecular descriptors encoding for the Molecular Electrostatic Potential (autoMEP), to simultaneously discriminate A(2A)R versus A(3)R antagonists and to predict their binding affinity to the corresponding receptor subtype of a large dataset of known pyrazolo-triazolo-pyrimidine analogs. To validate our approach, we have synthetized 51 new pyrazolo-triazolo-pyrimidine derivatives anticipating both A(2A)R/A(3)R subtypes selectivity and receptor binding affinity profiles.
- Subjects :
- Binding Sites
Drug Discovery
Humans
Models, Chemical
Protein Binding
Pyrazoles chemical synthesis
Pyrazoles chemistry
Pyrazoles pharmacology
Pyrimidines chemical synthesis
Receptor, Adenosine A2A chemistry
Receptor, Adenosine A3 chemistry
Static Electricity
Structure-Activity Relationship
Triazoles chemical synthesis
Triazoles chemistry
Triazoles pharmacology
Adenosine A2 Receptor Antagonists
Adenosine A3 Receptor Antagonists
Artificial Intelligence
Pyrimidines chemistry
Pyrimidines pharmacology
Receptor, Adenosine A2A metabolism
Receptor, Adenosine A3 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 17
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 19501513
- Full Text :
- https://doi.org/10.1016/j.bmc.2009.05.038