Recent advances in protein conformation sampling by combining machine learning with molecular simulation

Abstract

Abstract The rapid advancement and broad application of machine learning (ML) have driven a groundbreaking revolution in computational biology. One of the most cutting-edge and important applications of ML is its integration with molecular simulations to improving the sampling efficiency of the vast conformational space of large biomolecules. This review focuses on recent studies that utilize ML-based techniques in the exploration of protein conformational landscape. We first highlight the recent development of ML-aided enhanced sampling methods, including heuristic algorithms and neural networks that are designed to refine the selection of reaction coordinates for the construction of bias potential, or facilitate the exploration of the unsampled region of the energy landscape. Further, we review the development of autoencoder based methods which combine molecular simulations and deep learning to expand the search of protein conformations. Lastly, we discuss the cutting-edge methodologies for the one-shot generation of protein conformations with precise Boltzmann weights. Collectively, this review demonstrates the promising potential of machine learning in revolutionizing our insight into the complex conformational ensembles of proteins.