Emulating Docking Results Using a Deep Neural Network: A New Perspective for Virtual Screening.

Docking is one of the most important steps in virtual screening pipelines, and it is an established method for examining potential interactions between ligands and receptors. However, this method is computationally expensive, and it is often among the last steps of the process of compound libraries evaluation. In this work, we investigate the feasibility of learning a deep neural network to predict the docking output directly from a two-dimensional compound structure. The developed protocol is orders of magnitude faster than typical docking software, and it returns ligand-receptor complexes encoded in the form of the interaction fingerprint. Its speed and efficiency unlock the application possibilities, such as screening compound libraries of vast size on the basis of contact patterns or docking score (derived on the basis of predicted interaction schemes). We tested our approach on several G protein-coupled receptor targets and 4 CYP enzymes in retrospective virtual screening experiments, and a variant of graph convolutional network appeared to be most effective in emulating docking results. The method can be easily used by the community based on the code available in the Supporting Information.

Substructural Connectivity Fingerprint and Extreme Entropy Machines-A New Method of Compound Representation and Analysis.

Key-based substructural fingerprints are an important element of computer-aided drug design techniques. The usefulness of the fingerprints in filtering compound databases is invaluable, as they allow for the quick rejection of molecules with a low probability of being active. However, this method is flawed, as it does not consider the connections between substructures. After changing the connections between particular chemical moieties, the fingerprint representation of the compound remains the same, which leads to difficulties in distinguishing between active and inactive compounds. In this study, we present a new method of compound representation-substructural connectivity fingerprints (SCFP), providing information not only about the presence of particular substructures in the molecule but also additional data on substructure connections. Such representation was analyzed by the recently developed methodology-extreme entropy machines (EEM). The SCFP can be a valuable addition to virtual screening tools, as it represents compound structure with greater detail and more specificity, allowing for more accurate classification.

The importance of standardisation - COVID-19 CT & Radiograph Image Data Stock for deep learning purpose.

With the number of affected individuals still growing world-wide, the research on COVID-19 is continuously expanding. The deep learning community concentrates their efforts on exploring if neural networks can potentially support the diagnosis using CT and radiograph images of patients' lungs. The two most popular publicly available datasets for COVID-19 classification are COVID-CT and COVID-19 Image Data Collection. In this work, we propose a new dataset which we call COVID-19 CT & Radiograph Image Data Stock. It contains both CT and radiograph samples of COVID-19 lung findings and combines them with additional data to ensure a sufficient number of diverse COVID-19-negative samples. Moreover, it is supplemented with a carefully defined split. The aim of COVID-19 CT & Radiograph Image Data Stock is to create a public pool of CT and radiograph images of lungs to increase the efficiency of distinguishing COVID-19 disease from other types of pneumonia and from healthy chest. We hope that the creation of this dataset would allow standardisation of the approach taken for training deep neural networks for COVID-19 classification and eventually for building more reliable models.

Mol-CycleGAN: a generative model for molecular optimization.

Designing a molecule with desired properties is one of the biggest challenges in drug development, as it requires optimization of chemical compound structures with respect to many complex properties. To improve the compound design process, we introduce Mol-CycleGAN-a CycleGAN-based model that generates optimized compounds with high structural similarity to the original ones. Namely, given a molecule our model generates a structurally similar one with an optimized value of the considered property. We evaluate the performance of the model on selected optimization objectives related to structural properties (presence of halogen groups, number of aromatic rings) and to a physicochemical property (penalized logP). In the task of optimization of penalized logP of drug-like molecules our model significantly outperforms previous results.