Predicting subtype selectivity of dopamine receptor ligands with three-dimensional biologically relevant spectrum
| Autor: | De-Xin Kong, Shi-Yu Feng, Dong Wang, Ben Hu, Song-Bing He, Zheng-Kun Kuang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Quantitative structure–activity relationship Support Vector Machine Correlation coefficient Quantitative Structure-Activity Relationship Machine learning computer.software_genre Ligands Biochemistry Spectrum (topology) Receptors Dopamine 03 medical and health sciences Similarity (network science) Molecular descriptor Drug Discovery Pharmacology Chemistry business.industry Organic Chemistry Regression analysis Pattern recognition Support vector machine 030104 developmental biology Models Chemical Dopamine receptor Molecular Medicine Artificial intelligence business computer |
| Zdroj: | Chemical biologydrug design. 88(6) |
| ISSN: | 1747-0285 |
| Popis: | We applied a novel molecular descriptor, three-dimensional biologically relevant spectrum (BRS-3D), in subtype selectivity prediction of dopamine receptor (DR) ligands. BRS-3D is a shape similarity profile calculated by superimposing the objective compounds against 300 template ligands from sc-PDB. First, we constructed five subtype selectivity regression models between DR subtypes D1-D2, D1-D3, D2-D3, D2-D4, and D3-D4. The models' 10-fold cross-validation-squared correlation coefficient (Q2 , for training sets) and determination coefficient (R2 , for test sets) were in the range of 0.5-0.7 and 0.6-0.8, respectively. Then, four pair-wise (D1-D2, D2-D3, D2-D4, and D3-D4) and a multitype (D2, D3, and D4) classification models were developed with the prediction accuracies around or over 90% (for test sets). Lastly, we compared the performances of the models developed on BRS-3D and classical descriptors. The results showed that BRS-3D performed similarly to classical 2D descriptors and better than other 3D descriptors. Combining BRS-3D and 2D descriptors can further improve the prediction performance. These results confirmed the capacity of BRS-3D in the prediction of DR subtype-selective ligands. |
| Databáze: | OpenAIRE |
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