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Light-sensitive Proteins

Light detection is a common capability of different organisms, that dedicate to this purpose a specific class of proteins, namely photoreceptors. Small organic molecules, known as chromophores are bound to these proteins, to make the first task in the light transduction pathway. For istance, in rhodopsin, upon absorption of a photon, the chromophore (the Retinal Protonated Schiff Base) undergo a photochemical reactions going from 11-cis to all trans conformation. This changes are subsequently transmitted to the surrounding protein which serve as "biological amplifier" and initiates the signal transduction cascade. To correctly describe the behavior of chromophores during and upon light absorption, a Quantum Mechanics (QM) description is required. We use a mixed QM/MM scheme treating the chromophore at the QM level (using the Density Functional Theory), whereas the rest of the protein environment and solution at the Molecular Mechanics (MM) level.

Molecular Dynamics of Light Harvesting Complexes

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The Peridinin­ - Chlorophyll a - Protein (PCP) is a light-harvesting complex that works as antenna in the photosynthetic process of dinoflagellates. Its function is to collect incoming light also in the range where chlorophyll does not absorb, thanks to the peridinin molecules. In the protein each non­-equivalent peridinin molecule has absorption peaks at different wavelengths and can transfer the absorbed energy to chlorophyll. This spectra modulation, which has the fundamental functional role to extend the absorption spectra of the light harvesting complex, is originated by a combined effect of the distorted conformation and of the protein field. Recent high resolution X­-ray diffraction data on a reconstructed PCP, the refolded peridinin­ - chlorophyll a - protein (RFPCP) [1], opened the way to the mechanistic understanding of peridinin spectral tuning, peridinin­-chlorophyll energy transfer and photoprotective mechanisms [2]. RFPCP consist of two symmetric domains, each one binding a cluster of different cofactors: one chlorophyll a molecule, four peridinin molecules and one digalactosyldiacylglycerol (DGD) molecule. The high carotenoid:chlorophyll ratio (4:1) makes PCP unique among the light­-harvesting systems and assigns to peridinin an important role in the energy transfer mechanism. We perform classical molecular dynamics simulations of the RFPCP in explicit water solution: we analyse the structure and dynamics of the full protein and of its pigments to investigate the role of the four non­-equivalent peridinins in the protein function. We perform also electronic structure calculations (QM/MM) to study the Triplet Excitation Energy Transfer (TEET) mechanism [3] between the chlorophyll and one of the peridinin molecules.  

1 T. Schulte, D. M. Niedzwiedzki, R. R. Birge, R. G. Hiller, T. Polivka, E. Hofmann, and H. A. Frank, PNAS 106, 20764­20769 (2009).
2 A. Damjanovic, T. Ritz and K. Schulten, Biophysical Journal, 79, 1695­1705 (2000).
3 M.T.A. Alexandre, D.C. Lührs, I.H.M. von Stokkum, R. Hiller, M.L. Groot, J.T.M. Kennis, R. van Grondelle, Biophysical Journal, 93, 2118-2128 (2007).


                                   A                                                                                          B



A) Arrangement of the QM/MM system: the MM part (thin line) includes the backbone (blue) and the cofactors (red); the QM box (bold line) contains one chlorophyll (green) and one peridinin (orange)

B) Localization of the spin density (difference between the density of the spin_up and spin_down orbitals) for the triplet state of chlorophyll (green) and peridinin (orange)


A Minimal Model of the Retinal by Many Body Perturbation Theory

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The very first step of the mechanism of vision in animals is the photoisomerization, caused by the absorption of a photon, of the Retinal located inside the rhodopsin in the retina of eyes.
This process has been studied both experimentally and theoretically with the help of model photo-active molecules. Thanks to its small dimensions and common features of the isomerization pathway with the Retinal, the Protonated Schiff Base Minimal Model (C5H6NH+2 ), is the most studied model. In collaboration with Adriano Mosca Conte, Rodolfo Del Sole and Olivia Pulci at Univ. of Rome "Tor Vergata", we investigate its optical properties along the isomerization pathway by ab-initio calculations based on Many-Body Perturbation Theory (MBPT): GWmethod and the Bethe-Salpeter equation. The MBPT calculations agrees with post-Hartree Fock and Quantum Monte Carlo calculations and confirm a two-state model interpretation of the Minimal Model photo-isomerization. TDDFT outcomes qualitatively differ from these results.



The Photoactive Yellow Protein

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Photoactive Yellow Protein (PYP) is a small globular protein that activate negative phototaxis in purple sulphur bacterium Ectothiorhodospira halophila. The photosensitive component of PYP is a 4-hydroxycynnamic acid, also known as p-coumaric acid (pCA), chromophore covalently bound through a thioester linkage to the sole cysteine of the protein. To better understand the role of the environment in the absorption and emission properties and on the dynamics of the PYP chromophore, different experimental and theoretical studies have been addressed to reduced model chromophores.
We investigated the room temperature ground and excited state properties of different PYP modelchromophores both in vacuo and in water solution by means of QM/MM simulations. Four different molecular models of the PYP chromophore were considered: pCA-n (neutral p-coumaric acid in vacuo), pCA-a (anionic p-coumaric acid in vacuo), TMpCA-a (thio-methyl p-coumaric acid in vacuo), and TMpCA-a-sol (thio-methyl p-coumaric acid in QM/MM water solution). The absorption spectra can be calculated by averaging snapshots from ab initio MD both in vacuo and in QM/MM solution (see figure below).



                                                The calculated absorption spectra during ab initio molecular dynamics symulations of PYP
                                            chromophore models in vacuo and in solution. pCA-n/a (neutral/anionic pcoumaric acid in gas phase),
                                                             TMpCA-a (anionic thio-methyl pCA in gas phase and in solution)

In a similar manner, the absorption spectra of the full PYP protein in solution can be calculated and compared with the available experimental results. 
On the basis of these computer simulations we are investigating at the molecular level the interplay between absorption spectra, molecular geometries and solvent (or protein) environment in the Photoactive Yellow Protein and in its synthetic chromophore analogues.



Molecular Biophysics of Vision

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The understanding of the molecular mechanisms involved in light detection is an challenging task for the science of vision, that has important implication from both the medical and technological point of views. The first step in the eye detection of light is the photo-excitation of the receptor cells (rod and cones) in the retina. The rod cells, responsible for the peripheral and night vision, accomplish this function using as a fundamental detector the integral membrane protein rhodopsin (Fig. A). In normal conditions, photons excite the rhodopsin chromophore moiety, the retinal, inducing a cis to trans isomerization (Fig. B) that provokes allosteric changes in the protein. These modification causes G-protein binding at the rhodopsin cytoplasmic side, triggering a complex signal transduction cascade of signalling, finally leading to neuronal signal and vision. The failures of proper synthesis, processing or functioning of this signal transduction machinary are involved in the pathogenesis of many eyes diseases, such as the class of hereditary progressive blinding diseases Retinis Pigmentosa.



 A) The rhodopsin protein is represented by light blue tubes and ribbons whereas its photoactive moiety (the retinal chromophore) is represented by yellow sticks. 
 B) The rodopsin retinal protonated Schiff base undertakes a 11-cis to all-trans isomerization upon photon absorption. 


In the first femtoseconds of their photocycle, the retinal are isomerized by light absorption around a C-C double bond, leading to local change in the protein surroundings. The initial movements are therefore transmitted to the protein-wide scale, and converted in significant structural changes and biological signal. With classical MD, QM/MM, and TDDFT we have investigated the very first movements upon light absorption as well as the subsequent protein relaxation [10,14,17].


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