Development of a Neural Network-Based Approach for Prediction of Potential HIV-1 Entry Inhibitors Using Deep Learning and Molecular Modeling Methods

A generative adversarial autoencoder for the rational design of potential HIV-1 entry inhibitors able to block the region of the viral envelope protein gp120 critical for the virus binding to cellular receptor CD4 was developed using deep learning methods. In doing so, the following studies were carried out: (i) the architecture of the neural network was constructed; (ii) a virtual compound library of potential anti-HIV-1 agents for training the neural network was formed; (iii) molecular docking of all compounds from this library with gp120 was made and calculations of the values of binding free energy were performed; (iv) molecular fingerprints for chemical compounds from the training dataset were generated; (v) training the neural network was implemented followed by estimation of the learning outcomes and work of the autoencoder. The validation of the neural network on a wide range of compounds from the ZINC database was carried out. The use of the neural network in combination with virtual screening of chemical databases was shown to form a productive platform for identifying the basic structures promising for the design of novel antiviral drugs that inhibit the early stages of HIV infection.