QCexplore · Quantum Chemical Exploration of Reaction Networks: From Origins of Life to De Novo Enzyme Design

Gaining comprehensive insights into chemical and biochemical reaction networks is crucial for understanding and controlling molecular and catalytic processes; however, unraveling their intricate mechanisms remains a key challenge. QCexplore will provide a generally applicable solution to this challenge by developing an unbiased quantum-chemical reaction network exploration method and a highly efficient, fully automated open-source software framework.The starting point for these developments is our proof-of-concept approach of a computational hyperreactor introduced in 2024. By integrating reactivity-enhancing concepts – such as external acceleration of system components and elevation of the potential energy surface (hyperdynamics) – with fast, linear-scaling quantum-chemical methods, QCexplore’s framework will enable efficient and unbiased exploration of reaction networks under fully controlled and realistic conditions. The incorporation of novel data mining techniques, along with efficient refinement procedures, will allow for effective navigation and analysis of the reaction network’s data for identifying relevant reaction pathways. In this way, QCexplore overcomes traditional, manual and error-prone approaches to reaction mechanism elucidation.The performance of QCexplore’s developed framework will be demonstrated by tackling key questions in origins of life research, such as how essential molecular building blocks are formed and combined to create larger aggregates like RNA strands. Further, it will be applied to lay a robust foundation for de novo enzyme design by accurately identifying the key steps in catalytic processes, determining dominant reaction pathways, and uncovering strategies to enhance enzymatic activity and selectivity. The demonstrated versatility of the QCexplore framework is expected to open new avenues for the interplay between theory and experiment.