Hybrid QM/classical models: Methodological advances and new applications

Hybrid methods that combine quantum mechanical descriptions with classical models are very popular in molecular modeling. Such a large diffusion reflects their effectiveness, which over the years has allowed the quantum mechanical description to extend its boundaries to systems of increasing size and to processes of increasing complexity. Despite this success, research in this field is still very active and a number of advances have been made recently, further extending the range of their applications. In this review, we describe such advances and discuss how hybrid methods may continue to improve in the future. The various formulations proposed so far are presented here in a coherent way to underline their common methodological aspects. At the same time, the specificities of the different classical models and of their coupling with the quantum mechanical domain are highlighted and discussed, with special attention to the computational and numerical aspects

Delocalized excitons in natural light harvesting complexes

Natural organisms such as photosynthetic bacteria, algae, and plants employ complex molecular machinery to convert solar energy into biochemical fuel. An important common feature shared by most of these photosynthetic organisms is that they capture photons in the form of excitons typically delocalized over a few to tens of pigment molecules embedded in protein environments of light harvesting complexes (LHCs). Delocalized excitons created in such LHCs remain well protected despite being swayed by environmental fluctuations, and are delivered successfully to their destinations over hundred nanometer length scale distances in about hundred picosecond time scales. Decades of experimental and theoretical investigation have produced a large body of information offering insights into major structural, energetic, and dynamical features contributing to LHCs' extraordinary capability to harness photons using delocalized excitons. The objective of this review is (i) to provide a comprehensive account of major theoretical, computational, and spectroscopic advances that have contributed to this body of knowledge, and (ii) to clarify the issues concerning the role of delocalized excitons in achieving efficient energy transport mechanisms. The focus of this review is on three representative systems, Fenna-Matthews-Olson complex of green sulfur bacteria, light harvesting 2 complex of purple bacteria, and phycobiliproteins of cryptophyte algae. Although we offer more in-depth and detailed description of theoretical and computational aspects, major experimental results and their implications are also assessed in the context of achieving excellent light harvesting functionality. Future theoretical and experimental challenges to be addressed in gaining better understanding and utilization of delocalized excitons are also discussed.Comment: 53 pages, 15 figure

A fast method for electronic couplings in embedded multichromophoric systems

: Electronic couplings are key to understanding exciton delocalization and transport in natural and artificial light harvesting processes. We develop a method to compute couplings in multichromophoric aggregates embedded in complex environments without running expensive quantum chemical calculations. We use a transition charge approximation to represent the quantum mechanical transition densities of the chromophores and an atomistic and polarizable classical model to describe the environment atoms. We extend our framework to estimate transition charges directly from the chromophore geometry, i.e., bypassing completely the quantum mechanical calculations using a regression approach. The method allows to rapidly compute accurate couplings for a large number of geometries along molecular dynamics trajectories

Electronic Excitations in Nonpolar Solvents: Can the Polarizable Continuum Model Accurately Reproduce Solvent Effects?

In nonpolar solvents, both electrostatic and nonelectrostatic interactions play a role in tuning the electronic excitations of molecular solutes. This specificity makes the application of continuum solvation models a challenge. Here, we propose a strategy for the calculation of solvatochromic shifts on absorption spectra, using a coupling of the polarizable continuum model with a time-dependent density functional theory framework, which explicitly accounts for dispersion and repulsion, as well as for electrostatic effects. Our analysis makes a step further in the interpretation of the effects of nonpolar solvents and suggests new directions in their modeling using continuum formulations

Excitonic Nature of Carotenoid-Phthalocyanine Dyads and Its Role in Transient Absorption Spectra

Artificial carotenoid-tetrapyrrole dyads have been extensively used as model systems to understand the quenching mechanisms that occur in light-harvesting complexes during nonphotochemical quenching. In particular, dyads containing a carotenoid covalently linked to a zinc phthalocyanine have been studied by transient absorption spectroscopy, and the observed signals have been interpreted in terms of an excitonically coupled state involving the lowest excited states of the two fragments. If present, such excitonic delocalization would have significant implications on the mechanism of nonphotochemical quenching. Here, we use quantum chemical calculations to show that this delocalization is not needed to reproduce the transient absorption spectra. On the contrary, the observed signals can be explained through excitonic couplings in the higher-energy manifold of states. We also argue that the covalent linkage between the two fragments allows for electronic communications, which complicates the analysis of the spectra based on two independent but coupled moieties. These findings call for a more thorough reassessment of the photophysics in these dyads and its implications in the context of natural nonphotochemical quenching

Excited state gradients within a polarizable QM/MM formulation

Multiscale approaches that partition the system into an active site (where the electronic process under study occurs) and a remaining region, the environment, have proven to be good strategies for the computation of electronic excitations in complex systems. In this work the implementation of a polarizable QM/MM scheme for the computation of excited state gradients is presented and are applied to a test case

Computational Investigation of Structural and Spectroscopic Properties of LOV-Based Proteins with Improved Fluorescence

Flavin-based fluorescent proteins are a class of fluorescent reporters derived from light, oxygen, and voltage (LOV) sensing proteins. Through mutagenesis, natural LOV proteins have been engineered to obtain improved fluorescence properties. In this study, we combined extended classical Molecular Dynamics simulations and multiscale Quantum Mechanics/Molecular Mechanics methods to clarify the relationship between structural and dynamic changes induced by specific mutations and the spectroscopic response. To reach this goal we compared two LOV variants, one obtained by the single mutation needed to photochemically inactivate the natural system, and the other (iLOV) obtained through additional mutations and characterized by a significantly improved fluorescence. Our simulations confirmed the "flipping and crowding" effect induced in iLOV by the additional mutations and revealed its mechanism of action. We also showed that these mutations, and the resulting differences in the composition and flexibility of the binding pockets, are not reflected in significant shifts of the excitation and emission energies, in agreement with the similarity of the spectra measured for the two systems. However, a small but consistent reduction was found in the Stokes shift of iLOV, suggesting a reduction of the intermolecular reorganization experienced by the chromophore after excitation, which could slow down its internal conversion to the ground state and improve the fluorescence

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 Rhodomonas 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

Molecular Mechanisms of Activation in the Orange Carotenoid Protein Revealed by Molecular Dynamics

Light-harvesting in photosynthesis is accompanied by photoprotective processes. In cyanobacteria, the photoprotective role is played by a specialized complex, the orange carotenoid protein, which is activated by strong blue-green light. This photoactivation involves a unique series of structural changes which terminate with an opening of the complex into two separate domains, one of which acts as a quencher for the light-harvesting complexes. Many experimental studies have tried to reveal the molecular mechanisms through which the energy absorbed by the carotenoid finally leads to the large conformational change of the complex. Here, for the first time, these mechanisms are revealed by simulating at the atomistic level the whole dynamics of the complex through an effective combination of enhanced sampling techniques. On the basis of our findings, we can conclude that the carotenoid does not act as a spring that, releasing its internal strain, induces the dissociation, as was previously proposed, but as a "latch" locking together the two domains. The photochemically triggered displacement of the carotenoid breaks this balance, allowing the complex to dissociate