Microbial natural products represent a major source of bioactive compounds for drug discovery. Among these molecules, nonribosomal peptides (NRPs) represent a diverse class that include antibiotics, immunosuppressants, anticancer agents, toxins, siderophores, pigments, and cytostatics. The discovery of novel NRPs remains a laborious process because many NRPs consist of nonstandard amino acids that are assembled by nonribosomal peptide synthetases (NRPSs). Adenylation domains (A-domains) in NRPSs are responsible for selection and activation of monomers appearing in NRPs. During the past decade, several support vector machine-based algorithms have been developed for predicting the specificity of the monomers present in NRPs. These algorithms utilize physiochemical features of the amino acids present in the A-domains of NRPSs. In this article, we benchmarked the performance of various machine learning algorithms and features for predicting specificities of NRPSs and we showed that the extra trees model paired with one-hot encoding features outperforms the existing approaches. Moreover, we show that unsupervised clustering of 453 560 A-domains reveals many clusters that correspond to potentially novel amino acids. While it is challenging to predict the chemical structure of these amino acids, we developed novel techniques to predict their various properties, including polarity, hydrophobicity, charge, and presence of aromatic rings, carboxyl, and hydroxyl groups.

Recent work in the literature has shown experimentally that one can use the lower layers of a trained convolutional neural network (CNN) to model natural textures. More interestingly, it has also been experimentally shown that only one layer with random filters can also model textures although with less variability. In this paper we ask the question as to why one layer CNNs with random filters are so effective in generating textures? We theoretically show that one layer convolutional architectures (without a non-linearity) paired with the an energy function used in previous literature, can in fact preserve and modulate frequency coefficients in a manner so that random weights and pretrained weights will generate the same type of images. Based on the results of this analysis we question whether similar properties hold in the case where one uses one convolution layer with a non-linearity. We show that in the case of ReLu non-linearity there are situations where only one input will give the minimum possible energy whereas in the case of no nonlinearity, there are always infinite solutions that will give the minimum possible energy. Thus we can show that in certain situations adding a ReLu non-linearity generates less variable images.