Molecular Dynamics of Polymer-lipids in Solution from Supervised Machine Learning

TL;DR

This study evaluates recurrent neural networks for predicting the energetics of polymer-lipid systems in molecular dynamics simulations, finding limited success with individual models but improved results using an ensemble approach that better captures energy fluctuations.

Contribution

The paper introduces an ensemble-based protocol to enhance neural network predictions of molecular energetics, addressing limitations of single models in reproducing fluctuation distributions.

Findings

Recurrent neural networks have limited ability to reproduce energy fluctuations.

Ensemble methods improve forecast consistency with molecular dynamics data.

Single models struggle to match the distribution of energy fluctuations.

Abstract

Machine learning techniques including neural networks are popular tools for materials and chemical scientists with applications that may provide viable alternative methods in the analysis of structure and energetics of systems ranging from crystals to biomolecules. However, efforts are less abundant for prediction of dynamics. Here we explore the ability of three well established recurrent neural network architectures for forecasting the energetics of a macromolecular polymer-lipid aggregate solvated in ethyl acetate at ambient conditions. Data models generated from recurrent neural networks are trained and tested on nanoseconds-long time series of the intra-macromolecules potential energy and their interaction energy with the solvent generated from Molecular Dynamics and containing half million points. Our exhaustive analyses convey that the three recurrent neural network investigated generate data models with limited capability of reproducing the energetic fluctuations and yielding short or long term energetics forecasts with underlying distribution of points inconsistent with the input series distributions. We propose an in silico experimental protocol consisting on forming an ensemble of artificial network models trained on an ensemble of series with additional features from time series containing pre-clustered time patterns of the original series. The forecast process improves by predicting a band of forecasted time series with a spread of values consistent with the molecular dynamics energy fluctuations span. However, the distribution of points from the band of forecasts is not optimal. Although the three inspected recurrent neural networks were unable of generating single models that reproduce the actual fluctuations of the inspected molecular system energies in thermal equilibrium at the nanosecond scale, the proposed protocol provides useful estimates of the molecular fate