Natural Product Scores and Fingerprints Extracted from Artificial Neural Networks

Due to their desirable properties, natural products are an important ligand class for medicinal chemists. However, due to their structural distinctiveness, traditional cheminformatic approaches, like ligand-based virtual screening, often perform worse for natural products. Based on our recent work, we evaluated the ability of neural networks to generate fingerprints more appropriate for use with natural products. A manually curated dataset of natural products and synthetic decoys was used to train a multi-layer perceptron network and an autoencoder-like network. In-depth analysis showed that the extracted natural product-specific neural fingerprint outperforms traditional as well as natural product-specific fingerprints on three datasets. Further, we explored how the activations from the output layer of a network can work as a novel natural product likeness score. Overall, two natural product-specific datasets were generated, which are publicly available together with the code to create the fingerprints and the novel natural product likeness score.