Facilitating Transition State Search with Minimal Conformational Sampling Using Reaction Graph.

Abstract

Elucidating transition states (TSs) is crucial for understanding chemical reactions. The reliability of traditional TS search approaches depends on input conformations that require significant effort to prepare. Previous automated methods for generating input reaction conformations typically involve extensive exploration of a large conformational space. Such exhaustive search can be complicated by the rapid growth of the conformational space, especially for reactions involving many rotatable bonds, multiple reacting molecules, and numerous bond formations and dissociations. To address this problem, we propose a new approach that generates reaction conformations for TS searches with minimal reliance on sampling. This method constructs a pseudo-TS structure based on a reaction graph containing bond formation and dissociation information and modifies it to produce reactant and product conformations. Tested on three different benchmarks, our method consistently generated suitable conformations without necessitating extensive sampling, demonstrating its potential to significantly improve the applicability of automated TS searches. This approach offers a valuable tool for a broad range of applications such as reaction mechanism analysis and network exploration.