Structural and quantum chemical basis for OCP-mediated quenching of phycobilisomes.

Cyanobacteria use large antenna complexes called phycobilisomes (PBSs) for light harvesting. However, intense light triggers non-photochemical quenching, where the orange carotenoid protein (OCP) binds to PBS, dissipating excess energy as heat. The mechanism of efficiently transferring energy from phycocyanobilins in PBS to canthaxanthin in OCP remains insufficiently understood. Using cryo-electron microscopy, we unveiled the OCP-PBS complex structure at 1.6- to 2.1-angstrom resolution, showcasing its inherent flexibility. Using multiscale quantum chemistry, we disclosed the quenching mechanism. Identifying key protein residues, we clarified how canthaxanthin's transition dipole moment in its lowest-energy dark state becomes large enough for efficient energy transfer from phycocyanobilins. Our energy transfer model offers a detailed understanding of the atomic determinants of light harvesting regulation and antenna architecture in cyanobacteria.

The OpenMMPol library for polarizable QM/MM calculations of properties and dynamics.

We present a new library designed to provide a simple and straightforward way to implement QM/AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications) and other polarizable QM/MM (Molecular Mechanics) methods based on induced point dipoles. The library, herein referred to as OpenMMPol, is free and open-sourced and is engineered to address the increasing demand for accurate and efficient QM/MM simulations. OpenMMPol is specifically designed to allow polarizable QM/MM calculations of ground state energies and gradients and excitation properties. Key features of OpenMMPol include a modular architecture facilitating extensibility, parallel computing capabilities for enhanced performance on modern cluster architectures, a user-friendly interface for intuitive implementation, and a simple and flexible structure for providing input data. To show the capabilities offered by the library, we present an interface with PySCF to perform QM/AMOEBA molecular dynamics, geometry optimization, and excited-state calculation based on (time-dependent) density functional theory.

Unraveling Water Solvation Effects with Quantum Mechanics/Molecular Mechanics Semiclassical Vibrational Spectroscopy: The Case of Thymidine.

We introduce a quantum mechanics/molecular mechanics semiclassical method for studying the solvation process of molecules in water at the nuclear quantum mechanical level with atomistic detail. We employ it in vibrational spectroscopy calculations because this is a tool that is very sensitive to the molecular environment. Specifically, we look at the vibrational spectroscopy of thymidine in liquid water. We find that the C═O frequency red shift and the C═C frequency blue shift, experienced by thymidyne upon solvation, are mainly due to reciprocal polarization effects, that the molecule and the water solvent exert on each other, and nuclear zero-point energy effects. In general, this work provides an accurate and practical tool to study quantum vibrational spectroscopy in solution and condensed phase, incorporating high-level and computationally affordable descriptions of both electronic and nuclear problems.

Breaking the Rules: On the Relative Stability of Some Methylencyclopropane and Methylcyclopropene Derivatives.

The structure of the spirocyclic product obtained by reacting catechol with 1,1-dichloro-2-(chloromethyl)cyclopropane is shown by NMR and X-ray analysis to be that of a 2-methylcyclopropene (MeCP), instead of the previously reported 2-methylenecyclopropane (MCP) one. The study of the equilibration between the two isomeric forms by experimental and computational means (including both Density Functional Theory - DFT - and Coupled Cluster with single, double, and perturbative triple excitations - CCSD(T) - calculations) revealed that, at variance with most of the alkylidenecyclopropane/alkylcyclopropene systems described to date, for the compounds of the present study the MeCP derivative is more stable by≈ 2.5-3.0 Kcal mol-1 than the MCP one. The extension of the DFT and CCSD(T) study to other spiro-MCP/MeCP pairs suggests that the origin of the unexpected shift of the equilibrium position can be tracked back to a combination of electronic and ring-strain effects. These findings lead to re-think a long-standing, and substantially undisputed belief in the area of unsaturated cyclopropane derivatives.

Newton-X Platform: New Software Developments for Surface Hopping and Nuclear Ensembles.

Newton-X is an open-source computational platform to perform nonadiabatic molecular dynamics based on surface hopping and spectrum simulations using the nuclear ensemble approach. Both are among the most common methodologies in computational chemistry for photophysical and photochemical investigations. This paper describes the main features of these methods and how they are implemented in Newton-X. It emphasizes the newest developments, including zero-point-energy leakage correction, dynamics on complex-valued potential energy surfaces, dynamics induced by incoherent light, dynamics based on machine-learning potentials, exciton dynamics of multiple chromophores, and supervised and unsupervised machine learning techniques. Newton-X is interfaced with several third-party quantum-chemistry programs, spanning a broad spectrum of electronic structure methods.

Trajectory Surface Hopping for a Polarizable Embedding QM/MM Formulation.

We present the implementation of trajectory surface-hopping nonadiabatic dynamics for a polarizable embedding QM/MM formulation. Time-dependent density functional theory was used at the quantum mechanical level of theory, whereas the molecular mechanics description involved the polarizable AMOEBA force field. This implementation has been obtained by integrating the surface-hopping program Newton-X NS with an interface between the Gaussian 16 and the Tinker suites of codes to calculate QM/AMOEBA energies and forces. The implementation has been tested on a photoinduced electron-driven proton-transfer reaction involving pyrimidine and a hydrogen-bonded water surrounded by a small cluster of water molecules and within a large water droplet.

An enhanced sampling QM/AMOEBA approach: The case of the excited state intramolecular proton transfer in solvated 3-hydroxyflavone.

We present an extension of the polarizable quantum mechanical (QM)/AMOEBA approach to enhanced sampling techniques. This is achieved by connecting the enhanced sampling PLUMED library to the machinery based on the interface of Gaussian and Tinker to perform QM/AMOEBA molecular dynamics. As an application, we study the excited state intramolecular proton transfer of 3-hydroxyflavone in two solvents: methanol and methylcyclohexane. By using a combination of molecular dynamics and umbrella sampling, we find an ultrafast component of the transfer, which is common to the two solvents, and a much slower component, which is active in the protic solvent only. The mechanisms of the two components are explained in terms of intramolecular vibrational redistribution and intermolecular hydrogen-bonding, respectively. Ground and excited state free energies along an effective reaction coordinate are finally obtained allowing for a detailed analysis of the solvent mediated mechanism.

Excited States of Xanthophylls Revisited: Toward the Simulation of Biologically Relevant Systems.

Xanthophylls are a class of oxygen-containing carotenoids, which play a fundamental role in light-harvesting pigment-protein complexes and in many photoresponsive proteins. The complexity of the manifold of the electronic states and the large sensitivity to the environment still prevent a clear and coherent interpretation of their photophysics and photochemistry. In this Letter, we compare cutting-edge ab initio methods (CC3 and DMRG/NEVPT2) with time-dependent DFT and semiempirical CI (SECI) on model keto-carotenoids and show that SECI represents the right compromise between accuracy and computational cost to be applied to real xanthophylls in their biological environment. As an example, we investigate canthaxanthin in the orange carotenoid protein and show that the conical intersections between excited states and excited-ground states are mostly determined by the effective bond length alternation coordinate, which is significantly tuned by the protein through geometrical constraints and electrostatic effects.

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.

Polarizable embedding QM/MM: the future gold standard for complex (bio)systems?

Nowadays, hybrid QM/MM approaches are widely used to study (supra)molecular systems embedded in complex biological matrices. However, in their common formulation, mutual interactions between the quantum and classical parts are neglected. To go beyond such a picture, a polarizable embedding can be used. In this perspective, we focus on the induced point dipole formulation of polarizable QM/MM approaches and we show how efficient and linear scaling implementations have allowed their application to the modeling of complex biosystems. In particular, we discuss their use in the prediction of spectroscopies and in molecular dynamics simulations, including Born-Oppenheimer dynamics, enhanced sampling techniques and nonadiabatic descriptions. We finally suggest the theoretical and computational developments that still need to be achieved to overcome the limitations which have prevented so far larger diffusion of these methods.

Successes & challenges in the atomistic modeling of light-harvesting and its photoregulation.

Light-harvesting is a crucial step of photosynthesis. Its mechanisms and related energetics have been revealed by a combination of experimental investigations and theoretical modeling. The success of theoretical modeling is largely due to the application of atomistic descriptions combining quantum chemistry, classical models and molecular dynamics techniques. Besides the important achievements obtained so far, a complete and quantitative understanding of how the many different light-harvesting complexes exploit their structural specificity is still missing. Moreover, many questions remain unanswered regarding the mechanisms through which light-harvesting is regulated in response to variable light conditions. Here we show that, in both fields, a major role will be played once more by atomistic descriptions, possibly generalized to tackle the numerous time and space scales on which the regulation takes place: going from the ultrafast electronic excitation of the multichromophoric aggregate, through the subsequent conformational changes in the embedding protein, up to the interaction between proteins.