Benedetta Mennucci

• Doctor of Philosophy
• Professor (Full) at University of Pisa

Higher plants Photosystem I absorbs near-infrared light through long-wavelength chlorophylls, enriched under vegetation canopies, to enhance photon capture. Far-red absorption originates from chlorophylls pairs within the Lhca3 and Lhca4 subunits of the LHCI antenna, known as the “red cluster” composed of chlorophylls a603 and a609. - We used rever...

In this study, we evaluate the performance of two cost-effective models, namely, TD-DFT and ΔSCF methods, combined withdifferent molecular mechanics models, to predict the photophysical andphotochemical properties of a set of fluorescent mutants of the microbialrhodopsin Archaerhodopsin-3. We investigate absorption energies andexcited-state isomeri...

Photosynthetic organisms rely on a network of light-harvesting protein-pigment complexes to efficiently absorb sunlight and transfer excitation energy to reaction center proteins where charge separation occurs. In photosynthetic purple bacteria, these complexes are embedded within the cell membrane, with lipid composition affecting complex clusteri...

We present a polarizable embedding quantum mechanics/molecular mechanics (QM/MM) framework for ground‐ and excited‐state Complete Active Space Self‐Consistent Field (CASSCF) calculations on molecules within complex environments, such as biological systems. These environments are modeled using the AMOEBA polarizable force field. This approach is imp...

Naturally occurring photoenzymes are rare in nature, but among them, fatty acid photodecarboxylases derived from Chlorella variabilis (CvFAPs) have emerged as promising photobiocatalysts capable of performing the redox-neutral, light-induced decarboxylation of free fatty acids (FAs) into C1-shortened n-alka(e)nes. Using a hybrid QM/MM approach comb...

In this study, we evaluate the performance of two cost-effective models, namely TD-DFT and ∆SCF methods, combined with different Molecular Mechanics models, to predict photophysical and photochemical properties of a set of fluorescent mutants of the microbial rhodopsin Archaerhodopsin3. We investigate absorption energies and excited state isomeriza...

We present a polarizable embedding quantum mechanics/molecular mechanics (QM/MM) framework for ground- and excited-state Complete Active Space Self-Consistent Field (CASSCF) calculations on molecules within complex environments, such as biological systems. These environments are modeled using the AMOEBA polarizable force field. This approach is imp...

The application of quantum mechanics (QM)/molecular mechanics (MM) models for studying dynamics in complex systems is nowadays well established. However, their significant limitation is the high computational cost, which restricts their use for larger systems and long-timescale processes. We propose a machine-learning (ML) based approach to study t...

Stress exerted by excess captured light energy in cyanobacteria is prevented by the photoprotective activity of the orange carotenoid protein (OCP). Under high light, the OCP converts from an orange, inactive form (OCPO) into the red form (OCPR) that binds to and quenches the phycobilisome (PBS). Structurally, the OCP consists of two domains: the N...

Light-harvesting complexes (LHC) are known to regulate the flux of energy in different light conditions and activate quenching processes to prevent photodamage in case of high light. However, the molecular mechanisms behind these photoprotective processes remain unclear. A widely accepted model suggests an excitation-energy transfer from excited ch...

Naturally occurring photoenzymes are rare in nature, but among them, fatty acid photodecarboxylases derived from Chlorella variabilis (CvFAPs) have emerged as promising photobiocatalysts capable of performing redox-neutral, light-induced decarboxylation of free fatty acids (FAs) into C1-shortened n-alka(e)nes. This study focuses specifically on the...

The application of quantum mechanics (QM) / molecular mechanics (MM) models for studying dynamics in complex systems is nowadays well established. However, their significant limitation is the high computational cost, which restricts their use for larger systems and long-timescale processes. We propose a machine-learning (ML) based approach to study...

Bacteriophytochromes are light-sensing biological machines that switch between two photoreversible states, Pr and Pfr. Their relative stability is opposite in canonical and bathy bacteriophytochromes, but in both cases the switch between them is triggered by the photoisomerization of an embedded bilin chromophore. We applied an integrated multiscal...

Photosynthetic organisms rely on a network of light-harvesting protein-pigment complexes to efficiently absorb sunlight and transfer excitation energy to reaction center proteins for charge separation. In photosynthetic purple bacteria, these complexes are embedded in the cell membrane, where lipid composition affects their clustering and inter-com...

Solvatochromism occurs in both homogeneous solvents and more complex biological environments, such as proteins. While in both cases the solvatochromic effects report on the surroundings of the chromophore, their interpretation in proteins becomes more complicated not only because of structural effects induced by the protein pocket but also because...

Bacteriophytochromes are light-sensing biological machines that interconvert between two spectroscopically distinct states, Pr and Pfr. The relative stability of the two states is opposite in canonical and bathy bacteriophytochromes but in both cases the switch between them is triggered by a photoisomerization of an embedded bilin chromophore, the...

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...

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 rem...

Light-Harvesting Complex II (LHCII) is the major antenna of higher plants. Energy transfer processes taking place inside its aggregate of chlorophylls have been experimentally investigated with time-resolved techniques, but a complete understanding of the most relevant energy transfer pathways and relative characteristic times remains elusive. Theo...

Data-driven techniques are increasingly used to replace electronic-structure calculations of matter. In this context, a relevant question is whether machine learning (ML) should be applied directly to predict the desired properties or combined explicitly with physically grounded operations. We present an example of an integrated modeling approach i...

In plants, light-harvesting complexes serve as antennas to collect and transfer the absorbed energy to reaction centers, but also regulate energy transport by dissipating the excitation energy of chlorophylls. This process, known as nonphotochemical quenching, seems to be activated by conformational changes within the light-harvesting complex, but...

Solvatochromism occurs in both homogeneous solvents and more complex biological environments such as proteins. While in both cases the solvatochromic effects report on the surroundings of the chromophore, their interpretation in proteins becomes more complicated, not only because of structural effects induced by the protein pocket, but also because...

Carotenoid pigments are known to present a functional versatility when bound to light-harvesting complexes. This versatility originates from a strong correlation between a complex electronic structure and a flexible geometry that is easily tunable by the surrounding protein environment. Here, we investigated how the different L1 and L2 sites of the...

Light-harvesting complexes (LHCs) of plants serve as antennas to collect light and transfer the absorbed energy to reaction centers, but also regulate energy transport by dissipating the excitation energy of chlorophylls. This process, known as nonphotochemical quenching (NPQ), seems to be activated by conformational changes within the LHCs, but th...

Carotenoid pigments are known to present a functional versatility when bound to light-harvesting complexes. This versatility originates from a strong correlation between a complex electronic structure and a flexible geometry which is easily tunable by the surrounding protein environment. Here, we investigated how the different L1 and L2 sites of th...

Cyanobacteria employ large antenna complexes called phycobilisomes (PBS) 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 r...

Orange Carotenoid Protein (OCP) is a ketocarotenoid-binding protein essential for photoprotection in cyanobacteria. The main steps of the photoactivated conversion which converts OCP from its resting state to the active one have been extensively investigated. However, the initial photochemical event in the ketocarotenoid which triggers the large st...

The antenna complexes of Photosystem I present low-lying states visible as red-shifted and broadened absorption and fluorescence bands. Among these, Lhca4 has the most evident features of these “red” states, with a fluorescence band shifted by more than 25 nm from typical LHC emission. This signal arises from a mixing of exciton and charge-transfer...

Orange Carotenoid Protein (OCP) is a ketocarotenoid-binding protein essential for photoprotection in cyanobacteria. The main steps of the photoactivated conversion which converts OCP from its resting state to the active one have been extensively investigated. However, the initial photochemical event in the ketocarotenoid which triggers the large st...

We describe the development, implementation, and application of a polarizable QM/MM strategy, based on the AMOEBA polarizable force field, for calculating molecular properties and performing dynamics of molecular systems embedded in complex matrices. We show that polarizable QM/MM is a well‐understood, mature technology that can be deployed using a...

In response to varying light conditions, light-harvesting complexes (LHCs) switch from a light-harvesting state to a quenched state to protect the photosynthetic organism from excessive light irradiation in a strategy known as nonphotochemical quenching (NPQ). NPQ is activated by an acidification of the thylakoid lumen, which is sensed directly or...

Phytochromes belong to a group of photoreceptor proteins containing a covalently bound biliverdin chromophore that inter-converts between two isomeric forms upon photoexcitation. The existence and stability of the photocycle products are largely determined by the protein sequence and the presence of conserved hydrogen-bonding interactions in the vi...

The excited-state dynamics of molecules embedded in complex (bio)matrices is still a challenging goal for quantum chemical models. Hybrid QM/MM models have proven to be an effective strategy, but an optimal combination of accuracy and computational cost still has to be found. Here, we present a method which combines the accuracy of a polarizable em...

We propose a machine learning (ML)-based strategy for an inexpensive calculation of excitonic properties of light-harvesting complexes (LHCs). The strategy uses classical molecular dynamics simulations of LHCs in their natural environment in combination with ML prediction of the excitonic Hamiltonian of the embedded aggregate of pigments. The propo...

In response to varying light conditions, light-harvesting complexes (LHCs) switch from a light-harvesting to a quenched state to protect the photosynthetic organism from excessive light irradiation, in a strategy known as nonphotochemical quenching (NPQ). NPQ is activated by an acidification of the thylakoid lumen which is sensed directly or indire...

Phytochromes are ubiquitous photoreceptors responsible for sensing light in plants, fungi and bacteria. Their photoactivation is initiated by the photoisomerization of the embedded chromophore, triggering large conformational changes in the protein. Despite numerous experimental and computational studies, the role of chromophore-protein interaction...

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 thes...

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 b...

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 thes...

Phytochromes are ubiquitous photoreceptors responsible for sensing light in plants, fungi and bacteria. Their photoactivation is initiated by the photoisomerization of the embedded bilin chromophore, which triggers a large conformational change in the protein. The initial photoisomerization and the following structural changes propagating from the...

We present the implementation of trajectory surface hopping nonadiabatic dynamics for a polarizable embedding QM/MM formulation. The time-dependent density functional theory has been used as the quantum mechanical level of theory, whereas the molecular mechanics description has involved the polarizable AMOEBA force field. This implementation has be...

Carotenoids are natural pigments with multiple roles in photosynthesis. They act as accessory pigments by absorbing light where chlorophyll absorption is low, and they quench the excitation energy of neighboring chlorophylls under high-light conditions. The function of carotenoids depends on their polyene-like structure, which controls their excite...

Hybrid TDDFT/MM approaches are very popular methods for describing electronic transitions of molecules in solution or embedded in more complex (bio)matrices. However, when combined with a polarisable force field some problems can appear depending on the type of environment response scheme that is used. In particular, specific a posteriori correctio...

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 th...

Non-local analogues of Auger decay are increasingly recognized as important relaxation processes in the condensed phase. Here, we explore non-local autoionization, specifically Intermolecular Coulombic Decay (ICD), of a series of aqueous-phase isoelectronic cations following 1s core-level ionization. In particular, we focus on Na+, Mg2+, and Al3+ i...

The function of light-harvesting complexes is determined by a complex network of dynamic interactions among all the different components: the aggregate of pigments, the protein, and the surrounding environment. Complete and reliable predictions on these types of composite systems can be only achieved with an atomistic description. In the last few d...

Phytochromes are photoreceptors responsible for sensing light in plants, fungi and bacteria. Their photoactivation is initiated by the photoisomerization of an embedded chromophore, which triggers a large conformational change in the structure of the entire protein. Although phytochromes have been subject of numerous studies, the photoisomerization...

Light-harvesting complexes (LHCs) are pigment-protein complexes whose main function is to capture sunlight and transfer the energy to reaction centers of photosystems. In response to varying light conditions, LH complexes also play photoregulation and photoprotection roles. In algae and mosses, a sub-family of LHCs, light-harvesting complex stress-...

Although the photophysics of BODIPY compounds has been widely investigated in the last few years, their analogues N-BODIPY compounds, with nitrogen substitution at the boron center, did not receive comparable attention. In this work we report their synthesis and photochemical characterization of a substituted N-BODIPY compound, by means of a combin...

In the last few decades, quantum chemistry has moved from simple molecules made of few atoms to large supramolecular aggregates embedded in complex environments. This significant change has been made possible by the important progress achieved by multiscale models and, in particular, those combining quantum mechanical (QM) descriptions and classica...

Light-harvesting complexes of plants exert a dual function of light-harvesting (LH) and photoprotection through processes collectively called nonphotochemical quenching (NPQ). While LH processes are relatively well characterized, those involved in NPQ are less understood. Here, we characterize the quenching mechanisms of CP29, a minor LHC of plants...

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 t...

Light-harvesting complexes (LHCs) are pigment-protein complexes whose main function is to capture sunlight and transfer the energy to reaction centers of photosystems. In response to varying light conditions, LH complexes also play photoregulation and photoprotection roles. In algae and mosses, a sub-family of LHCs, Light-Harvesting complex stress...

Photoreceptor proteins bind a chromophore, which, upon light absorption, modifies its geometry or its interactions with the protein, finally inducing the structural change needed to switch the protein from an inactive to an active or signaling state. In the Blue Light-Using Flavin (BLUF) family of photoreceptors, the chromophore is a flavin and the...

Ultrafast transient infrared (TRIR) spectroscopy is widely used to measure the excitation-induced structural changes of protein-bound chromophores. Here, we design a novel and general strategy to compute TRIR spectra of photoreceptors by combining μs-long MM molecular dynamics with ps-long QM/AMOEBA Born-Oppenheimer molecular dynamics (BOMD) trajec...

We present the implementation of a fully coupled polarizable QM/MM/continuum model based on the AMOEBA polarizable force field and the domain decomposition implementation of the conductor-like screening model. Energies, response properties, and analytical gradients with respect to both QM and MM nuclear positions are available, and a generic, atomi...

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...

Xanthophylls are an important class of oxygen containing carotenoids, which play a fundamental role both in light harvesting pigment-protein complexes and in many other photo-responsive 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...

Xanthophylls are an important class of oxygen containing carotenoids, which play a fundamental role both in light harvesting pigment-protein complexes and in many other photo-responsive 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...

div>Light-harvesting complexes (LHCs) of plants exert a dual function of light-harvesting and photoprotection. While LH processes are relatively well characterized, those involved in photoprotection are less understood. The main mechanism involved in photoprotection is to dissipate the energy absorbed by chlorophylls into harmless heat through proc...

div>Photoreceptor proteins bind a chromophore, which, upon light absorption, modifies its geometry or its interactions with the protein, finally inducing the structural change needed to switch the protein from an inactive to an active or signaling state. In the Blue Light-Using Flavin (BLUF) family of photoreceptors, the chromophore is a flavin and...

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 p...

Phytochromes are red-light sensing proteins, with important light-regulatory roles in different organisms, which are capturing an increasing interest in bioimaging and optogenetics. Upon absorption of light by the embedded bilin chromophore, they undergo structural changes that extend from the chromophore to the protein and finally drive the biolog...

Carotenoids are essential constituents of plant light-harvesting complexes (LHCs), being involved in protein stability, light harvesting, and photoprotection. Unlike chlorophylls, whose binding to LHCs is known to require coordination of the central magnesium, carotenoid binding relies on weaker intermolecular interactions (such as hydrogen bonds a...

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 Mechanic...

Multiscale models combining quantum mechanical and classical descriptions are a very popular strategy to simulate properties and processes of complex systems. Many alternative formulations have been developed, and they are now available in all of the most widely used quantum chemistry packages. Their application to the study of light-driven process...

Phytochromes are red-light sensing proteins, with important light-regulatory roles in different organisms, which are capturing an increasing interest in bioimaging and optogenetics. Upon absorption of light by the embedded bilin chromophore, they undergo structural changes that extend from the chomophore to the protein and finally drive the biologi...

pre>Phytochromes are red-light sensing proteins, with important light-regulatory roles in different organisms, which are capturing an increasing interest in bioimaging and optogenetics. Upon absorption of light by the embedded bilin chromophore, they undergo structural changes that extend from the chomophore to the protein and finally drive the bio...

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 comple...

Lasers based on biological materials are attracting an increasing interest in view of their use in integrated and transient photonics. DNA as optical biopolymer in combination with highly-emissive dyes has been reported to have excellent potential in this respect, however achieving miniaturized lasing systems based on solid-state DNA shaped in diff...

Subsystem time-dependent density-functional theory (sTDDFT) making use of approximate non-additive kinetic energy (NAKE) functionals is known to be capable of describing excitation energy transfer processes in a variety of applications. Here, we show that sTDDFT, especially when combined with projection-based embedding (PbE), can be employed for th...

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...

Lasers based on biological materials are attracting an increasing interest in view of their use in integrated and transient photonics. Deoxyribonucleic acid (DNA) as optical biopolymer in combination with highly emissive dyes has been reported to have excellent potential in this respect. However, achieving miniaturized lasing systems based on solid...

We present the implementation of excited state Born-Oppenheimer molecular dynamics (BOMD) within a polarizable QM/MM approach based on a time-dependent Density Functional Theory (TDDFT) formulation and the AMOEBA force field. The implementation relies on an interface between Tinker and Gaussian software and it uses an algorithm for the calculation...

Antenna complexes in photosystems of plants and green algae are able to switch between a light-harvesting unquenched conformation and a quenched conformation so to avoid photodamage. When the switch is activated, nonphotochemical quenching (NPQ) mechanisms take place for an efficient deactivation of excess excitation energy. The molecular details o...

We present a fully atomistic simulation of linear optical spectra (absorption, fluorescence and circular dichroism) of the Light Harvesting Complex II (LHCII) trimer using an hybrid approach, which couples a quantum chemical description of the chlorophylls with a classical model for the protein and the external environment (membrane and water). The...

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 p...

We present a polarisable QM/MM investigation of NMR chemical shifts of a photoreceptor protein belonging to the Blue Light-Using Flavin family. Two different structures have been proposed for this photoreceptor which show a large variability in terms of the position and orientation of the protein residues around the flavin chromophore. Here, the tw...

We present the first comprehensive multiscale computational investigation of Resonance Raman (RR), absorption and Circular Dichroism (CD) spectra of the resting state of the dimeric phytochrome of Deinococcus radiodurans. The spectra are simulated in all their components, namely the energy position and the lineshapes of both the far-red and the blu...

The photosynthetic apparatus of higher plants can dissipate excess excitation energy during high light exposure, by deactivating excited chlorophylls through a mechanism called nonphotochemical quenching (NPQ). However, the precise molecular details of quenching and the mechanism regulating the quenching level are still not completely understood. F...

In this work the photophysics of four bichromophoric units was studied by means of static and time resolved spectroscopy, with the aim of disentangling the contribution of steric and electronic factors in regulating the efficiency of electronic energy transfer (EET). The newly synthesized dyads share the same acceptor moiety, a substituted BODIPY c...

Orange carotenoid protein (OCP) is a carotenoid-binding protein involved in photo-protection mechanisms of cyanobacteria. Upon exposure to high light, OCP interconverts from an orange resting form (OCP O) to a red active one (OCP R); the mechanism of this interconversion, even if extensively studied, has still not been fully elucidated. In this wor...

The light-harvesting in photosynthetic purple bacteria can be tuned in response to the light conditions during cell growth. One of the used strategy is to change the energy of the excitons in the major Light-Harvesting complex, commonly known as LH2. In the present study we report the first systematic investigation of the microscopic origin of the...

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...

Multichromophoric biosystems represent a broad family with very diverse members, ranging from light-harvesting pigment-protein complexes to nucleic acids. The former are designed to capture, harvest, efficiently transport, and transform energy from sunlight for photosynthesis, while the latter should dissipate the absorbed radiation as quickly as p...

In this work, we present the theory and implementation of the coupled cluster single and double excitations (CCSD) method combined with a classical polarizable molecular mechanics force field (MMPol) based on the induced dipole model. The method is developed to compute electronic excitation energies within the state specific (SS) and linear respons...