Marc de Wergifosse

The direct environment of a molecule modifies its ground-state, excited-state, and response properties, including geometry, energy, dynamics, and reactivity. For example, the theoretical description of solvatochromism should involve a realistic representation of the molecules surrounding the solute to faithfully reproduce experimental one- and two-photon absorption spectra (1PA and 2PA). The computational modelling of highly flexible systems, such as molecules in solution, requires the inclusion of dynamic structural effects. However, such treatments can be computationally prohibitive for large molecules or molecular assemblies, particularly at the quantum-mechanical level. Thanks to recent developments in simplified quantum chemistry (sQC) methods, Löffelsender and co-workers proposed all-atom quantum-mechanics (AQM) workflows to compute the 1PA and 2PA properties of molecules in realistic systems. The term “realistic systems” indicates that the calculations explicitly include large parts of the environment as well as dynamic structural effects, thereby providing model systems that are closer to reality. A first protocol, termed all-atom single-structure quantum mechanics (ASQM), was proposed for ultra-large systems using a single molecular structure and neglecting dynamic structural effects. An all-atom dynamic-structure quantum-mechanics (ADQM) protocol was subsequently proposed for more structurally dynamic systems, such as chromophores in solution. These workflows originally employed simplified time-dependent density functional theory with a tight-binding xTB ground state (sTD-DFT-xTB). In 2024, I introduced the eXact-integral sTD-DFT (XsTD-DFT) method, which removes the semi-empirical character of the sTD-DFT scheme by explicitly computing atomic-orbital two-electron integrals. It retains similar computational efficiency while improving agreement with conventional TD-DFT. In this contribution, the ASQM scheme is tested for computing the 1PA and 2PA properties of two proteins: bacteriorhodopsin and iLOV. The results show that the ASQM methodology can describe higher-energy transitions involving π-conjugated amino acids such as tryptophan and tyrosine. The ADQM workflow is then evaluated for reproducing the 1PA and 2PA spectra of flavin mononucleotide (FMN) in aqueous solution using snapshots obtained from GFN2-xTB molecular-dynamics simulations of explicitly solvated systems (ADQM-MD). Spectra computed with the ADQM-MD approach show striking agreement with experiment. Finally, the AQM methodologies are adapted to employ the XsTD-DFT method for computing excited states and response properties. Comparisons with experiment are presented for the 1PA and circular dichroism spectra of photoactive yellow protein (PYP), the NEXAFS spectra of a collagen model, and the absorption spectra of several dyes in solution.