GPCR molecular dynamics forecasting using recurrent neural networks

G protein-coupled receptors (GPCRs) are a large superfamily of cell membrane proteins that play an important physiological role as transmitters of extracellular signals. Signal transmission through the cell membrane depends on conformational changes in the transmembrane region of the receptor, which makes the investigation of the dynamics in these regions particularly relevant. Molecular dynamics (MD) simulations provide a wealth of data about the structure, dynamics, and physiological function of biological macromolecules by modelling the interactions between their atomic constituents. In this study, a Recurrent and Convolutional Neural Network (RNN) model, namely Long Short-Term Memory (LSTM), is used to predict the dynamics of two GPCR states and three specific simulations of each one, through their activation path and focussing on specific receptor regions. Active and inactive states of the GPCRs are analysed in six scenarios involving APO, Full Agonist (BI 167107) and Partial Inverse Agonist (carazolol) of the receptor. Four Machine Learning models with increasing complexity in terms of neural network architecture are evaluated, and their results discussed. The best method achieves an overall RMSD lower than 0.139 angstrom and the transmembrane helices are the regions showing the minimum prediction errors and minimum relative movements of the protein.