DataSheet1_Unraveling the role of thermal fluctuations on the exciton structure of the cryptophyte PC612 and PC645 photosynthetic antenna complexes.pdf

Protein scaffolds play a crucial role in tuning the light harvesting properties of photosynthetic pigment-protein complexes, influencing pigment-protein and pigment-pigment excitonic interactions. Here, we investigate the influence of thermal dynamic effects on the protein tuning mechanisms of phycocyanin PC645 and PC612 antenna complexes of cryptophyte algae, featuring closed or open quaternary structures. We employ a dual molecular dynamics (MD) strategy that combines extensive classical MD simulations with multiple short Born-Oppenheimer quantum/molecular mechanical (QM/MM) simulations to accurately account for both static and dynamic disorder effects. Additionally, we compare the results with an alternative protocol based on multiple QM/MM geometry optimizations of the pigments. Subsequently, we employ polarizable QM/MM calculations using time-dependent density functional theory (TD-DFT) to compute the excited states, and we adopt the full cumulant expansion (FCE) formalism to describe the absorption and circular dichroism spectra. Our findings indicate that thermal effects have only minor impacts on the energy ladder in PC612, despite its remarkable flexibility owing to an open quaternary structure. In striking contrast, thermal effects significantly influence the properties of PC645 due to the absence of a hydrogen bond controlling the twist of ring D in PCB β82 bilins, as well as the larger impact of fluctuations on the excited states of MBV pigments, which possess a higher conjugation length compared to other bilin types. Overall, the dual MD protocol combined with the FCE formalism yields excellent spectral properties for PC612 and PC645, and the resultant excitonic Hamiltonians pave the way for future investigations concerning the implications of open and closed quaternary structures on phycocyanin light harvesting properties.</p

Can Förster Theory Describe Stereoselective Energy Transfer Dynamics in a Protein–Ligand Complex?

Förster resonance energy transfer (FRET) reactions involving ligands and aromatic amino acids can substantially impact the fluorescence properties of a protein–ligand complex, an impact intimately related to the corresponding binding mode. Structural characterization of such binding events in terms of intermolecular distances can be done through the well-known R–6 distance-dependent Förster rate expression. However, such an interpretation suffers from uncertainties underlying Förster theory in the description of the electronic coupling that promotes FRET, mostly related to the dipole–dipole orientation factor, dielectric screening effects, and deviations from the ideal dipole approximation. Here, we investigate how Förster approximations impact the prediction of energy transfer dynamics in the complex between flurbiprofen (FBP) and human serum albumin (HSA), as well as a model FBP–Trp dyad, in which recent observation of enantioselective fluorescence quenching has been ascribed to energy transfer from FBP to Trp. To this end, we combine classical molecular dynamics simulations with polarizable quantum mechanics/molecular mechanics calculations that allow overcoming Förster approximations. On the basis of our results, we discuss the potential of structure-based simulations in the characterization of drug-binding events through fluorescence techniques. Overall, we find an excellent agreement between theory and experiment both in terms of enantioselectivity and FRET times, thus strongly supporting the reliability of the binding modes proposed for the (S) and (R) enantiomers of FBP. In particular, we show that the dynamic quenching arises from a small fraction of drug bound to the secondary site of HSA at the interface between subdomains IIA and IIB, whereas the enantioselectivity arises from the larger flexibility of the (S)-FBP enantiomer in the binding pocket

Toward a Molecular Scale Interpretation of Excitation Energy Transfer in Solvated Bichromophoric Systems

This paper presents a quantum-mechanical study of the intramolecular excitation energy transfer (EET) coupling in naphthalene-bridge-naphthalene systems in gas phase and in solution. ZINDO and TDDFT response schemes are compared using both an exact and an approximate solution. The approximate solution based on a perturbative approach uses the single chromophore properties to reconstruct the real system coupling thus neglecting possible through-bond effects which conversely are accounted for in the exact solution. The comparison of the results of the two approaches with the experiments allows a detailed analysis of the relative importance of through-bond and through-space effects as well as a more complete understanding of the modifications in the EET coupling with the size of the system, the chromophore−chromophore distance, and solvation

Theoretical Characterization of the Spectral Density of the Water-Soluble Chlorophyll-Binding Protein from Combined Quantum Mechanics/Molecular Mechanics Molecular Dynamics Simulations

Over the past decade, both experimentalists and theorists have worked to develop methods to describe pigment–protein coupling in photosynthetic light-harvesting complexes in order to understand the molecular basis of quantum coherence effects observed in photosynthesis. Here we present an improved strategy based on the combination of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations and excited-state calculations to predict the spectral density of electronic-vibrational coupling. We study the water-soluble chlorophyll-binding protein (WSCP) reconstituted with <i>Chl a</i> or <i>Chl b</i> pigments as the system of interest and compare our work with data obtained by Pieper and co-workers from differential fluorescence line-narrowing spectra (Pieper et al. J. Phys. Chem. B 2011, 115 (14), 4042−4052). Our results demonstrate that the use of QM/MM MD simulations where the nuclear positions are still propagated at the classical level leads to a striking improvement of the predicted spectral densities in the middle- and high-frequency regions, where they nearly reach quantitative accuracy. This demonstrates that the so-called “geometry mismatch” problem related to the use of low-quality structures in QM calculations, not the quantum features of pigments high-frequency motions, causes the failure of previous studies relying on similar protocols. Thus, this work paves the way toward quantitative predictions of pigment–protein coupling and the comprehension of quantum coherence effects in photosynthesis

Distance Dependence of Triplet Energy Transfer in Water and Organic Solvents: A QM/MD Study

The possibility to optimize optoelectronic devices, such as organic light-emitting diodes or solar cells, by exploiting the special characteristics of triplet electronic states and their migration ability is attracting increased attention. In this study, we analyze how an intervening solvent modifies the distance dependence of triplet electronic energy transfer (TEET) processes by combining molecular dynamics simulations with quantum chemical calculations of the transfer matrix elements using the Fragment Excitation Difference (FED) method. We determine the β parameter characterizing the exponential distance decay of TEET rates in a stacked perylene dimer in water, chloroform, and benzene solutions. Our results indicate that the solvent dependence of β (β_vacuum = 5.14 Å^–1 > β_water = 3.77 Å^–1 > β_chloroform = 3.61 Å^–1 > β_benzene = 3.44 Å^–1) can be rationalized adopting the McConnell model of superexchange, where smaller triplet energy differences between the donor and the solvent lead to smaller β constants. We also estimate the decay of hole transfer (HT) and excess electron transfer (EET) processes in the system using the Fragment Charge Difference (FCD) method and find that β_TEET can be reasonably well approximated by the sum of β_EET and β_HT constants

Spatial and Electronic Correlations in the PE545 Light-Harvesting Complex

The recent discovery of long-lasting quantum coherence effects in photosynthetic pigment–protein complexes has challenged our view of the role that protein motions play in light-harvesting processes. Several groups have suggested that correlated fluctuations involving the pigments site energies and couplings could be at the origin of such unexpected behavior. Here we combine molecular dynamics simulations with quantum mechanics/molecular mechanics calculations to analyze the degree of correlated fluctuations in the PE545 complex of <i>Rhodomonas</i> sp. strain CS24. We find that correlations between the motions of the chromophores, which are significantly assisted by the water solvent, do not translate into appreciable site energy correlations but do lead to significant cross-correlations of energies and couplings. Such behavior, not observed in a recent study on the Fenna–Mathews–Olson complex, seems to provide phycobiliproteins with an additional fundamental mechanism to control quantum coherence and light-harvesting efficiency compared with chlorophyll-containing complexes

Single Amino Acid Mutation Controls Hole Transfer Dynamics in DNA-Methyltransferase <i>Hha</i>I Complexes

Different mutagenic effects are generated by DNA oxidation that implies the formation of radical cation states (so-called holes) on purine nucleobases. The interaction of DNA with proteins may protect DNA from oxidative damage owing to hole transfer (HT) from the stack to aromatic amino acids. However, how protein binding affects HT dynamics in DNA is still poorly understood. Here, we report a computational study of HT in DNA complexes with methyltransferase <i>Hha</i>I with the aim of elucidating the molecular factors that explain why long-range DNA HT is inhibited when the glutamine residue inserted in the double helix is mutated into a tryptophan. We combine molecular dynamics, quantum chemistry, and kinetic Monte Carlo simulations and find that protein binding stabilizes the energies of the guanine radical cation states and significantly impacts the corresponding electronic couplings, thus determining the observed behavior, whereas the formation of a tryptophan radical leads to less efficient HT

How Solvent Controls Electronic Energy Transfer and Light Harvesting: Toward a Quantum-Mechanical Description of Reaction Field and Screening Effects

This paper presents a quantum-mechanical study of electronic energy transfer (EET) coupling on over 100 pairs of chromophores taken from photosynthetic light-harvesting antenna proteins. Solvation effects due to the protein, intrinsic waters, and surrounding medium are analyzed in terms of screening and reaction field contributions using a model developed recently that combines a linear response approach with the polarizable continuum model (PCM). We find that the screening of EET interactions is quite insensitive to the quantum-mechanical treatment adopted. In contrast, it is greatly dependent on the geometrical details (distance, shape, and orientation) of the chromophore pair considered. We demonstrate that implicit (reaction field) as well as screening effects are dictated mainly by the optical dielectric properties of the host medium, while the effect of the static properties is substantially less important. The empirical distance-dependent screening function we proposed in a recent letter (Scholes, G. D.; Curutchet, C.; Mennucci, B.; Cammi, R.; Tomasi, J. J. Phys. Chem. B 2007, 111, 6978−6982) is analyzed and compared to other commonly used screening factors. In addition, we show that implicit medium effects on the coupling, resulting from changes in the transition densities upon solvation, are strongly dependent on the particular system considered, thus preventing the possibility of defining a general empirical expression for such an effect

Electronic Couplings for Resonance Energy Transfer from CCSD Calculations: From Isolated to Solvated Systems

Quantum mechanical (QM) calculations of electronic couplings provide great insights for the study of resonance energy transfer (RET). However, most of these calculations rely on approximate QM methods due to the computational limitations imposed by the size of typical donor–acceptor systems. In this work, we present a novel implementation that allows computing electronic couplings at the coupled cluster singles and doubles (CCSD) level of theory. Solvent effects are also taken into account through the polarizable continuum model (PCM). As a test case, we use a dimer of indole, a common model system for tryptophan, which is routinely used as an intrinsic fluorophore in Förster resonance energy transfer studies. We consider two bright π → π* states, one of which has charge transfer character. Lastly, the results are compared with those obtained by applying TD-DFT in combination with one of the most popular density functionals, B3LYP

Examining Förster Energy Transfer for Semiconductor Nanocrystalline Quantum Dot Donors and Acceptors

Excitation energy transfer involving semiconductor quantum dots (QDs) has received increased attention in recent years because their properties, such as high photostability and size-tunable optical properties, have made QDs attractive as Förster resonant energy transfer (FRET) probes or sensors. An intriguing question in FRET studies involving QDs has been whether the dipole approximation, commonly used to predict the electronic coupling, is sufficiently accurate. Accurate estimates of electronic couplings between two 3.9 nm CdSe QDs and between a QD and a chlorophyll molecule are reported. These calculations are based on transition densities obtained from atomistic semiempirical calculations and time-dependent density functional theory for the QD and the chlorophyll, respectively. In contrast to the case of donor−acceptor molecules, where the dipole approximation breaks down at length scales comparable to the molecular dimensions, we find that the dipole approximation works surprisingly well when donor and/or acceptor is a spherical QD, even at contact donor−acceptor separations. Our conclusions provide support for the use of QDs as FRET probes for accurate distance measurements