Prediction of Protein-compound Binding Energies from Known Activity Data: Docking-score-based Method and its Applications.

ABSTRACT: 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 ma

SUBMITTER: Fukunishi Y 

PROVIDER: S-EPMC6055825 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature