Recent advances in the integration of protein mechanics and machine learning

Abstract

Mechanics underlies protein properties and behavior. From a theoretical standpoint, it is possible to derive these based on physical rules. This is appealing because they provide insights into physiology and disease, as well as aid in protein engineering; however, the convoluted nature of the biological system and current computational speeds limit its feasibility. Machine learning (ML) architectures are known for their ability to make inferences on complex data, such as the relationship between protein mechanics, properties, and behavior. Substantial efforts have been made to learn such correlations in tasks such as the prediction of structure, stability, natural frequency, mechanical strength, folding rate, solubility, and function. Each of these properties is interconnected through protein mechanics, and it is not surprising that the methods used in these tasks overlap highly in model input and architecture. In this review, we evaluate ML methods for the seven aforementioned prediction tasks to identify current trends in ML research in the field of protein sciences, focusing on the input and model architecture of each method. A short overview of de novo protein design is also provided. Finally, we highlight trends in the application of ML methods in the field of protein science, as well as directions for future improvements.