Density functional theory combined with molecular mechanics: the infrared spectra of flavin in solution.

The photophysics and photochemistry of flavin dyes determine the functional dynamics of a series of blue light photoreceptors that include the so-called BLUF (blue light sensors using flavin) domains. To enable molecular dynamics (MD) simulation studies of such signaling processes, we derived molecular mechanics (MM) models of flavin chromophores from density functional theory (DFT). Two 300 K ensembles of lumiflavin (LF) in aqueous solution were generated by extended MM-MD simulations using different MM potentials for the water. In a DFT/MM hybrid setting, in which LF was treated by DFT and the polarizing environment at atomistic resolution by MM, we applied instantaneous normal mode analyses (INMA) to these ensembles. From these data we determined the inhomogeneously broadened solution spectra as mixtures of Gaussian bands using a novel automated procedure for mode classification. Comparisons with vibrational spectra available in the literature on native and isotopically labeled flavins in aqueous solution serve us to determine suitable frequency scaling factors and to analyze the accuracy of our scaled DFT/MM-INMA approach. We show that our approach not only agrees with established computational descriptions but also extends such methods substantially by giving access to inhomogeneous line widths and band shapes.