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    Protein-Ligand Scoring with Convolutional Neural Networks

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    Computational approaches to drug discovery can reduce the time and cost associated with experimental assays and enable the screening of novel chemotypes. Structure-based drug design methods rely on scoring functions to rank and predict binding affinities and poses. The ever-expanding amount of protein-ligand binding and structural data enables the use of deep machine learning techniques for protein-ligand scoring. We describe convolutional neural network (CNN) scoring functions that take as input a comprehensive 3D representation of a protein-ligand interaction. A CNN scoring function automatically learns the key features of protein-ligand interactions that correlate with binding. We train and optimize our CNN scoring functions to discriminate between correct and incorrect binding poses and known binders and non-binders. We find that our CNN scoring function outperforms the AutoDock Vina scoring function when ranking poses both for pose prediction and virtual screening

    Why scoring functions cannot assess tail properties

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    Motivated by the growing interest in sound forecast evaluation techniques with an emphasis on distribution tails rather than average behaviour, we investigate a fundamental question arising in this context: Can statistical features of distribution tails be elicitable, i.e. be the unique minimizer of an expected score? We demonstrate that expected scores are not suitable to distinguish genuine tail properties in a very strong sense. Specifically, we introduce the class of max-functionals, which contains key characteristics from extreme value theory, for instance the extreme value index. We show that its members fail to be elicitable and that their elicitation complexity is in fact infinite under mild regularity assumptions. Further we prove that, even if the information of a max-functional is reported via the entire distribution function, a proper scoring rule cannot separate max-functional values. These findings highlight the caution needed in forecast evaluation and statistical inference if relevant information is encoded by such functionals.Comment: 18 page
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