Supervised machine learning approach to molecular dynamics forecast of SARS-CoV-2 spike glycoproteins at varying temperatures

Abstract: Molecular dynamics (MD) simulations are a widely used technique in modeling complex nanoscale interactions of atoms and molecules. These simulations can provide detailed insight into how molecules behave under certain environmental conditions. This work explores a machine learning (ML) solution to predicting long-term properties of SARS-CoV-2 spike glycoproteins (S-protein) through the analysis of its nanosecond backbone RMSD (root-mean-square deviation) MD simulation data at varying temperatures. The simulation data were denoised with fast Fourier transforms. The performance of the models was measured by evaluating their mean squared error (MSE) accuracy scores in recurrent forecasts for long-term predictions. The models evaluated include k-nearest neighbors (kNN) regression models, as well as GRU (gated recurrent unit) neural networks and LSTM (long short-term memory) autoencoder models. Results demonstrated that the kNN model achieved the greatest accuracy in forecasts with MSE scores over around 0.01 nm less than those of the GRU model and the LSTM autoencoder. Furthermore, it demonstrated that the kNN model accuracy increases with data size but can still forecast relatively well when trained on small amounts of data, having achieved MSE scores of around 0.02 nm when trained on 10,000 ns of simulation data. This study provides valuable information on the feasibility of accelerating the MD simulation process through training and predicting supervised ML models, which is particularly applicable in time-sensitive studies. Graphic abstract: SARS-CoV-2 spike glycoprotein molecular dynamics simulation. Extraction and denoising of backbone RMSD data. Evaluation of k-nearest neighbors regression, GRU neural network, and LSTM autoencoder models in recurrent forecasting for long-term property predictions.[Figure not available: see fulltext.].