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Prediction of Protein-compound Binding Energies from Known Activity Data: Docking-score-based Method and its Applications.
| Content Provider | Scilit |
|---|---|
| Author | Fukunishi, Yoshifumi Yamashita, Yasunobu Mashimo, Tadaaki Nakamura, Haruki |
| Copyright Year | 2018 |
| Description | Journal: Molecular Informatics We used protein-compound docking simulations to develop a structure-based quantitative structure-activity relationship (QSAR) model. The prediction model used docking scores as descriptors. The binding free energy was approximated by a weighted average of docking scores for multiple proteins. This approximation was based on a pharmacophore model of receptor pockets and compounds. The weights of the docking scores were restricted to small values to avoid unrealistic weights by a regularization term. Additional outlier elimination improved the results. We applied this method to two groups of targets. The first target was the kinase family. The cross-validation results of 107 kinase proteins showed that the RMSE of predicted binding free energies was 1.1 kcal/mol. The second target was the matrix metalloproteinase (MMP) family, which has been difficult for docking programs. MMPs require metal-binding groups in their inhibitor structures in many cases. A quantum effect contributes to the metal-ligand interaction. Despite this difficulty, the present method worked well for the MMPs. This method showed that the RMSE of predicted binding free energies was 1.1 kcal/mol. In comparison, with the original docking method the RMSE was 1.7 kcal/mol. The results suggest that the present QSAR model should be applied to general target proteins. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055825/pdf |
| e-ISSN | 18681751 |
| DOI | 10.1002/minf.201700120 |
| Journal | Molecular Informatics |
| Issue Number | 6-7 |
| Volume Number | 37 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2018-02-14 |
| Access Restriction | Open |
| Subject Keyword | Journal: Molecular Informatics Medicinal Chemistry Binding Free Energy Docking Score Protein−compound Docking |
| Content Type | Text |
| Resource Type | Article |
