Adaptive Transition State Refinement with Learned Equilibrium Flows

Abstract

Identifying transition states (TSs), the high-energy configurations that molecules pass through during chemical reactions, is essential for understanding and designing chemical processes. However, accurately and efficiently identifying these states remains one of the most challenging problems in computational chemistry. In this work, we introduce a new generative AI approach that improves the quality of initial guesses for TS structures. Our method can be combined with a variety of existing techniques, including both machine learning models and fast, approximate quantum methods, to refine their predictions and bring them closer to chemically accurate results. Applied to TS guesses from a state-of-the-art machine learning model, our approach reduces the median structural error to just 0.088 $\unicode{x212B}$ and lowers the median absolute error in reaction barrier heights to 0.79 kcal mol$^{-1}$. When starting from a widely used tight-binding approximation, it increases the success rate of locating valid TSs by 41\% and speeds up high-level quantum optimization by a factor of three. By making TS searches more accurate, robust, and efficient, this method could accelerate reaction mechanism discovery and support the development of new materials, catalysts, and pharmaceuticals.