Exploration of biochemical reactivity with a QM/MM growing string method

Abstract

In this work, we have implemented the single-ended growing string method using a hybrid internal/Cartesian coordinate scheme within our in-house QM/MM package, QoMMMa, representing the first implementation of the growing string method in the QM/MM framework. The goal of the implementation was to facilitate generation of QM/MM reaction pathways with minimal user input, and also to improve the quality of the pathways generated as compared to the widely used adiabatic mapping approach. We have validated the algorithm against a reaction which has been studied extensively in previous computational investigations – the Claisen rearrangement catalysed by chorismate mutase. The nature of the transition state and the height of the barrier was predicted well using our algorithm, where more than 88% of the pathways generated were deemed to be of production quality. Directly compared to using adiabatic mapping, we found that while our QM/MM single-ended growing string method is slightly less efficient, it readily produces reaction pathways with fewer discontinuites and thus minimises the need for involved remapping of unsatisfactory energy profiles.