TSNet: predicting transition state structures with tensor field networks and transfer learning

Abstract

Transition states are among the most important molecular structures in chemistry, critical to a variety of fields such as reaction kinetics, catalyst design, and the study of protein function. However, transition states are very unstable, typically only existing on the order of femtoseconds. The transient nature of these structures makes them incredibly difficult to study, thus chemists often turn to simulation. Unfortunately, computer simulation of transition states is also challenging, as they are first-order saddle points on highly dimensional mathematical surfaces. Locating these points is resource intensive and unreliable, resulting in methods which can take very long to converge. Machine learning, a relatively novel class of algorithm, has led to radical changes in several fields of computation, including computer vision and natural language processing due to its aptitude for highly accurate function approximation. While machine learning has been widely adopted throughout computational chemistry as a lightweight alternative to costly quantum mechanical calculations, little research has been pursued which utilizes machine learning for transition state structure optimization. In this paper TSNet is presented, a new end-to-end Siamese message-passing neural network based on tensor field networks shown to be capable of predicting transition state geometries. Also presented is a small dataset of S_N2 reactions which includes transition state structures – the first of its kind built specifically for machine learning. Finally, transfer learning, a low data remedial technique, is explored to understand the viability of pretraining TSNet on widely available chemical data may provide better starting points during training, faster convergence, and lower loss values. Aspects of the new dataset and model shall be discussed in detail, along with motivations and general outlook on the future of machine learning-based transition state prediction.