Multireference QM/MM Nonadiabatic Dynamics with Quantum Nuclei in Explicit Environment: Implementation in COBRAMM and Application to the Sub-100 fs Energy Transfer in NADH

We present a mixed quantum-classical framework for simulating nonadiabatic excited-state dynamics in explicit environments. The method combines a fully quantum-mechanical treatment of both electronic and nuclear degrees of freedom in the high-level (HL) region with classical propagation of the surrounding low-level (LL) environment. The HL dynamics is described using a linear vibronic coupling Hamiltonian parametrized at the multireference (XMS-CASPT2) level of theory, while bidirectional systembath coupling is incorporated through a dynamically updated electrostatic embedding scheme. The implementation, integrated into the COBRAMM suite, interfaces Quantics, OpenMolcas, and AMBER. Benchmark tests assess the stability, energy conservation, and approximations underlying the protocol. Among those, we highlight the crude adiabatic approximation, which allows to avoid explicit QM calculations for the update of the Hamiltonian during the dynamics, making the simulation time dependent only on the size of the active space required for the initial parametrization. As a proof of concept, we investigate the sub-100 fs excitation energy transfer (EET) in solvated NADH. Compared to simulations with a frozen environment, the explicit dynamical response of the solvent enhances the charge transfer (CT)-mediated EET pathway. The results highlight the critical role of fast librational solvent modes in ultrafast nonadiabatic phenomena and establish the presented protocol as a robust approach for treating environment-driven internal conversion in rigid photoresponsive molecular systems.