Narrow Results

Bayesian network (BN) is the well-accepted framework for representing and inferring uncertain knowledge. To learn the BN-based uncertain knowledge incrementally in response to the new data is useful for analysis, prediction, decision making, etc. In this paper, we propose an approach for incremental learning of BNs by focusing on the incremental revision of BN’s graphical structures. First, we give the concept of influence degree to describe the influence of new data on the existing BN by measuring the variation of BN’s probability parameters w.r.t. the likelihood of the new data. Then, for the nodes ordered decreasingly by their influence degrees, we give the scoring-based algorithm for revising BN’s subgraphs iteratively by hill-climbing search for reversing, adding or deleting edges. In the incremental revision, we emphasize the preservation of probabilistic conditional independencies implied in the BN based on the concept and properties of Markov equivalence. Experimental results show the correctness, precision and efficiency of our approach.

A descriptor, the pose scaling factor, is proposed to quantitatively evaluate the geometrical match between a ligand and a target binding site. The pose scaling factor can be used to readily rank results of target-based in silico database screening or docking on large numbers of compounds. Such an approach will be of utility in the development and refinement of docking algorithms.

Protein–ligand docking is a computational method to identify the binding mode of a ligand and a target protein, and predict the corresponding binding affinity using a scoring function. This method has great value in drug design. After decades of development, scoring functions nowadays typically can identify the true binding mode, but the prediction of binding affinity still remains a major problem. Here we present CScore, a data-driven scoring function using a modified Cerebellar Model Articulation Controller (CMAC) learning architecture, for accurate binding affinity prediction. The performance of CScore in terms of correlation between predicted and experimental binding affinities is benchmarked under different validation approaches. CScore achieves a prediction with R = 0.7668 and RMSE = 1.4540 when tested on an independent dataset. To the best of our knowledge, this result outperforms other scoring functions tested on the same dataset. The performance of CScore varies on different clusters under the leave-cluster-out validation approach, but still achieves competitive result. Lastly, the target-specified CScore achieves an even better result with R = 0.8237 and RMSE = 1.0872, trained on a much smaller but more relevant dataset for each target. The large dataset of protein–ligand complexes structural information and advances of machine learning techniques enable the data-driven approach in binding affinity prediction. CScore is capable of accurate binding affinity prediction. It is also shown that CScore will perform better if sufficient and relevant data is presented. As there is growth of publicly available structural data, further improvement of this scoring scheme can be expected.