QM/MM Study of the Monomeric Red Fluorescent Protein DsRed.M1

We report a combined quantum mechanical/molecular mechanical (QM/MM) study of the DsRed.M1 protein using as QM component the self-consistent charge density functional tight-binding (SCC-DFTB) method in molecular dynamics (MD) simulations and hybrid density functional theory (DFT, B3LYP functional) in QM/MM geometry optimizations. We consider different variants of the chromophore (including the cis- and trans-acylimine and peptide forms) as well as different protonation states of environmental residues. The QM/MM calculations provide insight into the role of nearby residues concerning their interactions with the chromophore and their influence on structural and spectroscopic properties. QM/MM optimizations yield a single conformer for the anionic acylimine chromophore, whereas there are distinct cis- and trans-conformers in the anionic peptide chromophore, the latter being more stable. The calculated vertical excitation energies (DFT/MRCI) for the anionic chromophores agree well with experiment. The published crystal structure of DsRed.M1 with an anionic acylimine chromophore indicates a quinoid structure, while the QM/MM calculations predict the phenolate form to be more stable

Electronically Excited States of Higher Acenes up to Nonacene: A Density Functional Theory/Multireference Configuration Interaction Study

While the optical spectra of the acene series up to pentacene provide textbook examples for the annulation principle, the spectra of the larger members are much less understood. The present work provides an investigation of the optically allowed excited states of the acene series from pentacene to nonacene, the largest acene observed experimentally, using the density functional based multireference configuration method (DFT/MRCI). For this purpose, the ten lowest energy states of the B_2u and B_3u irreducible representations were computed. In agreement with previous computational investigations, the electronic wave functions of the acenes acquire significant multireference character with increasing acene size. The HOMO → LUMO excitation is the major contributor to the ¹L_a state (p band, B_2u) also for the larger acenes. The oscillator strength decreases with increasing length. The ¹L_b state (α band, B_3u), so far difficult to assign for the larger acenes due to overlap with photoprecursor bands, becomes almost insensitive to acene length. The ¹B_b state (β band, B_3u) also moves only moderately to lower energy with increasing acene size. Excited states of B_3u symmetry that formally result from double excitations involving HOMO, HOMO–1, LUMO, and LUMO+1 decrease in energy much faster with system size. One of them (D1) has very small oscillator strength but becomes almost isoenergetic with the ¹L_a state for nonacene. The other (D2) also has low oscillator strength as long as it is higher in energy than ¹B_b. Once it is lower in energy than the ¹B_b state, both states interact strongly resulting in two states with large oscillator strengths. The emergence of two strongly absorbing states is in agreement with experimental observations. The DFT/MRCI computations reproduce experimental excitation energies very well for pentacene and hexacene (within 0.1 eV). For the larger acenes deviations are larger (up to 0.2 eV), but qualitative agreement is observed

Quantum Mechanics/Molecular Mechanics Insights into the Enantioselectivity of the <i>O-</i>Acetylation of (<i>R,S</i>)<i>-</i>Propranolol Catalyzed by Candida antarctica Lipase B

Classical molecular dynamics (MD) simulations and combined quantum mechanics/molecular mechanics (QM/MM) calculations were used to investigate the origin of the enantioselectivity of the Candida antarctica lipase B (CalB) catalyzed <i>O-</i>acetylation of (<i>R</i>,<i>S</i>)-propranolol. The reaction is a two-step process. The initial step is the formation of a reactive acyl enzyme (AcCalB) via a tetrahedral intermediate (TI-1). The stereoselectivity originates from the second step, when AcCalB reacts with the racemic substrate via a second tetrahedral intermediate (TI-2). Reaction barriers for the conversion of (<i>R</i>)<i>-</i> and (<i>S</i>)-propranolol to <i>O-</i>acetylpropranolol were computed for several distinct conformations of TI-2. In QM/MM geometry optimizations and reaction path calculations the QM region was described by density functional theory (B3LYP/TZVP) and the MM region by the CHARMM force field. The QM/MM calculations show that the formation of TI-2 is the rate-determining step. The energy barrier for transformation of (<i>R</i>)-propranolol to <i>O</i>-acetylpropranolol is 4.5 kcal/mol lower than that of the reaction of (<i>S</i>)-propranolol. Enzyme–substrate interactions were identified that play an important role in the enantioselectivity of the reaction. Our QM/MM calculations reproduce and rationalize the experimentally observed enantioselectivity in favor of (<i>R</i>)-propranolol. Furthermore, in contrast to what is commonly suggested for lipase-catalyzed reactions, our results indicate that the tetrahedral intermediate is not a good approximation of the corresponding transition states