Processes in solution: a journey from models to application

Hybrid quantum/classical (QM/MM) approaches, alongside other advanced multilayer computational schemes, combined with ab initio molecular dynamics (AIMD) have opened new doors for the structural and dynamic characterization of large macromolecular systems, including biomolecules in intricate environments. To achieve a high level of accuracy, it is crucial to account not only for the explicit interactions between the quantum mechanical and molecular mechanical components but also for the long-range interactions (bulk/matrix effects), which are essential for simulating realistic chemical processes. The ability to explicitly describe the solvent’s degrees of freedom, through atomistic modeling of a significant portion of the solvent, is essential for capturing the intricate interactions between solute and solvent.This approach is particularly important in systems where hydrogen bonding and other weak interactions play a central role in determining the system's properties. Ab initio simulations of solvated systems, in particular, require the employment of some boundary conditions, here we focus non-periodic (NPBC). By combining these elements - hierarchical QM/MM methods, AIMD, NPBC, and efficient phase-sampling schemes—scientists can achieve chemical accuracy in simulating ultra-fast time-resolved spectroscopy and photo-induced phenomena. This chapter provides a comprehensive overview of these methodologies, with a particular focus on the use of multi-layered approaches within the DFT framework and NPBC. Through detailed case studies, readers will gain a deep understanding of the power and versatility of these computational techniques, which are increasingly indispensable in the study of complex molecular systems. As we continue to push the boundaries of what is computationally possible, these methods promise to unlock new insights into the molecular world, with applications ranging from materials science to drug design and beyond.