RESUMEN

The early stages of the drug design process involve identifying compounds with suitable bioactivities via noisy assays. As databases of possible drugs are often very large, assays can only be performed on a subset of the candidates. Selecting which assays to perform is best done within an active learning process, such as batched Bayesian optimization, and aims to reduce the number of assays that must be performed. We compare how noise affects different batched Bayesian optimization techniques and introduce a retest policy to mitigate the effect of noise. Our experiments show that batched Bayesian optimization remains effective, even when large amounts of noise are present, and that the retest policy enables more active compounds to be identified in the same number of experiments.

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RESUMEN

The representation of the protein-ligand complexes used in building machine learning models play an important role in the accuracy of binding affinity prediction. The Extended Connectivity Interaction Features (ECIF) is one such representation. We report that (i) including the discretized distances between protein-ligand atom pairs in the ECIF scheme improves predictive accuracy, and (ii) in an evaluation using gradient boosted trees, we found that the resampling method used in selecting the best hyperparameters has a strong effect on predictive performance, especially for benchmarking purposes.