Topological Distance-Based Electron Interaction Tensor to Apply a Convolutional Neural Network on Drug-like Compounds.

Deep learning (DL) models in quantitative structure-activity relationship fed the molecular structure directly to the network without using human-designed descriptors by representing molecule as a graph or string (e.g., SMILES code). However, these two representations were oversimplification of real molecules to reflect chemical properties of molecular structures. Given that the choice of molecular representation determines the architecture of the DL model to apply, a novel way of molecular representation can open a way to apply diverse DL networks developed and used in other fields. A topological distance-based electron interaction (TDEi) tensor has been developed in this study inspired by the quantum mechanical model of the molecule, which defines a molecule with electrons and protons. In the TDEi tensor, the atomic orbital (AO) of each atom is represented by an electron configuration (EC) vector, which is a bit string based on the presence and absence of electrons in each AO according to spin indicated by positive and negative signs. Interactions between EC vectors were calculated based on the topological distance between atoms in a molecule. As a molecular structure was translated into 3D array, CNN models (modified VGGNet) were applied using a TDEi tensor to predict four physicochemical properties of drug-like compound datasets: MP (275,131), Lipop (4193), Esol (1127), and Freesolv (639). Models achieved good prediction accuracy. PCA showed that a stronger correlation was observed between the extracted features and the target endpoint as features were extracted from the deeper layer.