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In this work, we consider a new combination of vibrational analysis and normal-like mode decomposition of Debye-Waller factors of solvated ions entirely based on molecular dynamics data. Such a novel time-dependent analysis procedure provides a direct link between x-ray absorption fine structure parameters and normal mode contributions for an ion-solvent system. The potentialities of such a methodology rely on two fundamental aspects which distinguish it from already available tools. First, a general vibrational analysis that does not require any Gaussian or harmonic model for describing atomic fluctuations in liquids. Second, a very accurate sampling of the short range motions around the structural probe via the recently developed atom centered density matrix propagation/general liquid optimized boundary method. This novel molecular dynamics methodology is based on an integrated ab initio/classical potential using localized basis functions and nonperiodic boundary conditions. As a case study we have chosen the Zn(II) ion in aqueous solution. The consistency of our results and the observed good agreement with experiments show how the key support to advanced structural techniques from molecular dynamics can be further expanded and investigated. [ABSTRACT FROM AUTHOR]

In this work, we present a hybrid explicit/implicit solvation model, well suited for first-principles molecular dynamics simulations of solute-solvent systems. An effective procedure is presented that allows to reliably model a solute with a few explicit solvation shells, ensuring solvent bulk behavior at the boundary with the continuum. Such an approach is integrated with high-level ab initio methods using localized basis functions to perform first-principles or mixed quantum mechanics/molecular mechanics simulations within the extended-Lagrangian formalism. A careful validation of the model along with illustrative applications to solutions of acetone and glycine radical are presented, considering two solvents of different polarity, namely, water and chloroform. Results show that the present model describes dynamical and solvent effects with an accuracy at least comparable to that of conventional approaches based on periodic boundary conditions. [ABSTRACT FROM AUTHOR]

A novel molecular dynamics methodology recently proposed by our group [Rega et al., Chem. Phys. Lett. 422, 367 (2006)], which is based on an integrated hybrid potential rooted in high level quantum mechanical methods using localized basis functions and nonperiodic boundary conditions, has been applied to study acrolein in aqueous solution. The solute structural rearrangement and its hydrogen-bonding pattern due to the interactions with water have been analyzed in some detail. Moreover, the solvent effects on the UV n→π* vertical transition and on the NMR 13C and 17O shielding constants of acrolein have been investigated theoretically by performing a posteriori quantum mechanical calculations on a statistically significant number of snapshots extracted from both gas-phase and aqueous solution simulations. Results show that such effective computational strategy can be successfully used to improve our understanding, at atomic level, of important spectroscopic observables. [ABSTRACT FROM AUTHOR]

In this work, the mean field (MF) method, a continuum-based model designed for treating complex molecular systems, such as liquids and solutions, recently presented by Brancato et al. [J. Chem. Phys. 122, 154109 (2005)], has been further developed and improved especially in the treatment of the electrostatics. The revised model has been used to investigate the size effects on several physical properties of various solute-solvent systems by increasing the number of explicitly included solvent molecules from few tens up to thousands. Results on simple ions, such as sodium and chloride ions, and on a small peptide, such as alanine dipeptide analog (AcAlaNHMe), have shown that solvation structures and dynamics, as well as solvent-induced changes in the solute conformation, can be correctly reproduced by the MF model, providing that only two or three solvent layers are treated explicitly. [ABSTRACT FROM AUTHOR]

A multistate empirical valence bond model for proton transport in water, which explicitly includes solvent polarization, is presented. Polarization is included for each valence-bond state via induced point dipoles, and the model is parametrized to be used with an effective path integral derived potential surface, so as to include quantum effects of the transferring proton. The new model is shown to reproduce ab initio geometries and energetics for small protonated clusters. It is also shown that the new model gives a diffusion constant for the excess proton in water, which is in good agreement with experiment, and that the qualitative features of ab initio path integral simulations [D. Marx, M. E. Tuckerman, J. Hutter, and M. Parrinello, Nature (London) 397, 601 (1999)] are well reproduced. [ABSTRACT FROM AUTHOR]

In this paper we introduce a mean field method for simulating complex molecular systems like liquids and solutions. Using well-established theoretical principles and models, we obtained a relatively simple approach which seems to provide a reliable description of the bulk molecular behavior of liquid water. Moreover, we have applied this approach to study simple solutes in solution, like sodium and chloride ions and acetone. Comparison with standard simulations, performed with periodic boundary conditions, shows that such a mean field method can reproduce the same structural and thermodynamical properties at low computational costs and represents a valid alternative for simulating solute-solvent systems, like solutions of large biomolecules. [ABSTRACT FROM AUTHOR]

Dualfluorescence is an anomalous photophysical phenomenon observedin very few chromophores in which a two-color radiative process occursthat involves two distinct excited electronic states. To date itsobservation was linked either to electronic rearrangement of an excitedfluorophore leading to two conformers with distinct emissive properties,or to a photochemical modification leading to different fluorescentspecies. In both cases, emission originates from the lowest excitedstate of the resulting molecular configurations, in line with theso-called Kasha’s rule. We report here a combined theoreticaland spectroscopic study showing, for the first time, an anti-Kashadual-emission mechanism, in which simultaneous two-color emissiontakes place from the first and second excited state of a coumarinderivative. We argue that the observed environmental sensitivity ofthis peculiar optical response makes the present compound ideallysuited for biosensing applications in living cells. [ABSTRACT FROM AUTHOR]

Abstract: Radical species of the nucleic acid bases (NABs) play a primary role in radiation damage and electron transfer processes of DNA. In the present work, a novel QM/MM model for simulating molecular systems in the liquid phase has been applied to study the microsolvation of the uracil anion radical in comparison with the parent molecule. Moreover, we have analyzed the vertical detachment energy as a function of structural intramolecular and intermolecular fluctuations in order to find molecular modes that may possibly promote the electron transfer process. [Copyright &y& Elsevier]

Abstract: In the present work, the general liquid optimized boundary (GLOB) model, which is a discrete/continuum approach for molecular simulations of liquids and solutions, has been extended to include a pressure coupling algorithm based on an extended phase-space scheme. To this end, a definition of the instantaneous pressure for a microscopic system has been derived from the minimum energy principle for the Helmholtz free energy. Applications to a pure liquid, such as water, and an aqueous solution of myoglobin are presented and the results are compared to those obtained using standard periodic boundary conditions (PBC). [Copyright &y& Elsevier]

In this work, the GLOB model, an effective and reliable computational approach well suited for ab initio and QM/MM molecular dynamics simulations of complex molecular systems in solution, has been applied to study two representative open-shell systems, the cobalt(II) ion and the glycine radical in aqueous solution, with special reference to their structural and magnetic properties. The main structural features of the solvent cage around the cobalt ion and the hydrogen bonding patterns around the neutral and zwitterionic forms of the glycine radical have been investigated in some detail. The general good agreement with experiments supports the use of the present model to investigate more challenging and biological/technological relevant open-shell systems. [ABSTRACT FROM AUTHOR]

Abstract: The structural and electronic properties of the relatively long-lived (20μs) triplet state of acetone in aqueous solution have been studied using an effective QM/MM molecular dynamics approach (GLOB model) based on non-periodic boundary conditions and localized basis functions. In particular, the striking consequences of the n→π∗ electron promotion on the acetone structure and on its microsolvation have been analyzed in some detail and compared to the behaviour of the acetone ground-state. Moreover, the phosphorescence emission spectrum calculated on sampled molecular configurations, shows a Stokes shift in good agreement with available experimental data. [Copyright &y& Elsevier]

Abstract: A novel molecular dynamics methodology, which is based on an integrated ab initio/classical potential using localized basis functions and non-periodic boundary conditions, has been applied to study the microsolvation of the Zn(II) ion in aqueous solution. The metal ion, along with its first solvent shell, was treated at DFT B3LYP level, while the remaining bulk solvent was modeled with an effective TIP3P water model. The solvent structural arrangement around the ion has been analyzed and the characteristic Zn–O distance favourably compared to recent ND, XRD and EXAFS experiments, as well as to sophisticated cluster calculations. [Copyright &y& Elsevier]

A recently developed extended Lagrangian model employing localized basis functions and nonperiodic boundary conditions (GLOB/ADMP) was applied to the radicals issuing from the homolytic breaking of the Cα-Hα bond of glycine in aqueous solution at different pH values. Although the modifications of the structure and the magnetic properties of these species induced by the solvent are qualitatively reproduced by a static discrete-continuum model, magnetic parameters are further tuned by short-time dynamical effects (solute vibrations and solvent librations). The results delivered by GLOB/ADMP simulations for both hyperfine tensors and g-tensors are in remarkable agreement with their experimental counterparts, allowing a reliable disentanglement of the overall observables into well-defined contributions. The dominant role of out-of-plane vibrations in determining hyperfine splittings is confirmed and quantified, together with the remarkable sensitivity of the gyromagnetic tensor to bond lengths and valence angles defining the NCαC' moiety. Together with their specific interest for the title radical, our results suggest some interesting trends for other biologically significant radicals and point out the need of extending magneto-structural relationships to dynamical aspects. [ABSTRACT FROM AUTHOR]

In this work, we present an effective and flexible computational approach, which is the result of an on-going development conducted in our group, for simulating complex solute–solvent systems and computing relevant spectroscopic observables. Such an approach is based on QM/MM molecular dynamics techniques using non-periodic conductor boundary conditions and localized basis sets, combined with a posteriori high-level quantum mechanical methods for the calculation of spectroscopic parameters. As illustrative applications, we report structural and spectroscopic analyses of acetone, acrolein and glycine radical in aqueous solutions, where solvent effects on the NMR chemical shifts, UV absorption spectrum and EPR hyperfine coupling constants, respectively, are investigated and favorably compared to experimental measurements. In particular, it will be shown the importance of including dynamical effects in order to reproduce experimental data accurately. Moreover, we present an infrared analysis of formamide in both gas phase and acetonitrile from first-principle molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

Abstract: We describe the building blocks of an effective model employing localized basis functions and non-periodic boundary conditions for the treatment of solvent effects by ab initio molecular dynamics. After sketching the construction of a well sound hybrid potential in a first-principle dynamical framework, we validate the model for a diluted aqueous solution of chloride ion with special reference to the behaviour of different properties with the number of explicit water molecules. The reliability of the results and their stability well below 100 water molecules point out the interest of this new tool in the study of solvent effects. [Copyright &y& Elsevier]

Examines the occurrence of the information transmission in the supramolecular hydrogen bonding processes. Correlation between hydrogen bond directed assembly and symmetry distortion of macrocycles; Effects of hydrogen bonding template on reaction sites; Use of supramolecular-directed reactions in organic chemistry.

Examines the switching of the chirality expression in peptide rotaxanes. Inhibition of negative induced circular dichroism (CD) by peptido[2]rotaxanes; Elliptical polarization under switched off hydrogen bonding; Mechanism of generating the switchable CD response.

8-hydroxyquinoline-2-carboxylic acid (8-HQA) has been found in high concentrations (0.5–5.0 mmol·dm−3) in the gut of Noctuid larvae (and in a few other lepidopterans), in which it is proposed to act as a siderophore. Since it is known that many natural siderophores are also involved in the uptake and metabolism of other essential elements than iron, this study reports some results on the investigation of 8-HQA interactions with molybdate (MoO42−, i.e., the main molybdenum form in aqueous environments), in order to understand the possible role of this ligand as molybdophore. A multi-technique approach has been adopted, in order to derive a comprehensive set of information necessary to assess the chemical speciation of the 8-HQA/MoO42− system, as well as the coordination behavior and the sequestering ability of 8-HQA towards molybdate. Chemical speciation studies have been performed in KCl(aq) at I = 0.2 mol·dm−3 and T = 298.15 K by ISE-H+ (glass electrode) potentiometric and UV/Vis spectrophotometric titrations. CV (Cyclic Voltammetry), DP-ASV (Differential Pulse-Anodic Stripping Voltammetry), ESI-MS experiments and quantum mechanical calculations have been also performed to derive information about the nature and possible structure of species formed. These results are also compared with those reported for the 8-HQA/Fe3+ system in terms of chemical speciation and sequestering ability of 8-HQA. [ABSTRACT FROM AUTHOR]

In recent years, several tetracyanobuta‐1,3‐diene (TCBD) conjugates have been prepared by linking the tetracyano unit to various electroactive moieties. These push–pull conjugates, besides showing interesting physicochemical properties, are axially chiral, a feature arising from the restricted rotation around the central bond of the butadiene. Yet, only in a few cases, separation and isolation of the enantiomers have been successfully achieved, owing to the configurational lability of the corresponding enantiopure species. Herein, we report the first example of photo‐ and electroactive TCBD‐based derivatives showing unprecedented configurational stability and a peculiar light‐triggered enantiomer conversion mechanism enabled by triple‐state photogeneration. These systems represent a nice addition to the fast‐increasing arsenal of artificial, light‐controllable molecular switches. [ABSTRACT FROM AUTHOR]

In recent years, several tetracyanobuta‐1,3‐diene (TCBD) conjugates have been prepared by linking the tetracyano unit to various electroactive moieties. These push–pull conjugates, besides showing interesting physicochemical properties, are axially chiral, a feature arising from the restricted rotation around the central bond of the butadiene. Yet, only in a few cases, separation and isolation of the enantiomers have been successfully achieved, owing to the configurational lability of the corresponding enantiopure species. Herein, we report the first example of photo‐ and electroactive TCBD‐based derivatives showing unprecedented configurational stability and a peculiar light‐triggered enantiomer conversion mechanism enabled by triple‐state photogeneration. These systems represent a nice addition to the fast‐increasing arsenal of artificial, light‐controllable molecular switches. [ABSTRACT FROM AUTHOR]

Dispersion-inclusive density functional theory (DFT) methods have unequivocally demonstrated improved performances with respect to standard DFT approximations for modeling large and extended molecular systems at the quantum mechanical level. Yet, in some cases, disagreements with highly accurate reference calculations, such as CCSD(T) and quantum Monte Carlo (MC) calculations, still remain. Furthermore, the application of general-purpose corrections, such as the popular Grimme's semi-classical models (DFT-D), to different Kohn–Sham exchange–correlation functionals sometimes leads to variable and inconsistent results, which recommend a careful prior evaluation. In a recent study, we proposed a simple optimization protocol for enhancing the accuracy of these DFT-D methods by following an alternative and system-specific approach. Here, adopting the same computational strategy, we show how the accurate MC intermolecular interactions of a large set of water clusters of variable sizes (i.e., 300 (H2O)n structures, n = 9, 15, 27) can be reproduced remarkably well by dispersion-corrected DFT models (i.e., B3LYP-D4, PBE-D4, revPBE(0)-D4) upon re-optimization, reaching a mean absolute error per monomer of ~0.1 kcal/mol. Hence, the obtained results support the use of this procedure for fine-tuning tailored DFT-D models for the accurate description of targeted molecular systems. [ABSTRACT FROM AUTHOR]

Pentameric ligand gated ion channels (pLGICs) are ionotropic receptors that mediate fast intercellular communications at synaptic level and include either cation selective (e.g., nAChR and 5-HT3) or anion selective (e.g., GlyR, GABAA and GluCl) membrane channels. Among others, 5-HT3 is one of the most studied members, since its first cloning back in 1991, and a large number of studies have successfully pinpointed protein residues critical for its activation and channel gating. In addition, 5-HT3 is also the target of a few pharmacological treatments due to the demonstrated benefits of its modulation in clinical trials. Nonetheless, a detailed molecular analysis of important protein features, such as the origin of its ion selectivity and the rather low conductance as compared to other channel homologues, has been unfeasible until the recent crystallization of the mouse 5-HT3A receptor. Here, we present extended molecular dynamics simulations and free energy calculations of the whole 5-HT3A protein with the aim of better understanding its ion transport properties, such as the pathways for ion permeation into the receptor body and the complex nature of the selectivity filter. Our investigation unravels previously unpredicted structural features of the 5-HT3A receptor, such as the existence of alternative intersubunit pathways for ion translocation at the interface between the extracellular and the transmembrane domains, in addition to the one along the channel main axis. Moreover, our study offers a molecular interpretation of the role played by an arginine triplet located in the intracellular domain on determining the characteristic low conductance of the 5-HT3A receptor, as evidenced in previous experiments. In view of these results, possible implications on other members of the superfamily are suggested. [ABSTRACT FROM AUTHOR]

Tetracyanobuta‐1,3‐diene (TCBD) is a powerful and versatile electron‐acceptor moiety widely used for the preparation of electroactive conjugates. While many reports addressing its electron‐accepting capability have appeared in the literature, significantly scarcer are those dealing with its chemical modification, a relevant topic which allows to broaden the chemical space of this interesting functional unit. Here, we report on the first example of a high‐yielding cyano‐Diels‐Alder (CDA) reaction between TCBD, that is, where a nitrile group acts as a dienophile, and an anthryl moiety, that is, acting as a diene. The resulting anthryl‐fused‐TCBD derivative, which structure was unambiguously identified by X‐ray diffraction, shows high thermal stability, remarkable electron‐accepting capability, and interesting electronic ground‐ and excited‐state features, as characterized by a thorough theoretical, electrochemical, and photophysical investigation. Moreover, a detailed kinetic analysis of the intramolecular CDA reaction transforming the anthryl‐TCBD‐based reactant into the anthryl‐fused‐TCBD product was carried out at different temperatures. [ABSTRACT FROM AUTHOR]

An integrated computational approach built on quantum mechanical (QM) methods, purposely tailored inter- and intra-molecular force fields and continuum solvent models combined with time-independent and time-dependent schemes to account for nuclear motion effects is applied to the spectroscopic investigation of pyrimidine in the gas phase as well as in aqueous and CCl solutions. Accurate post-Hartree-Fock methodologies are employed to compute molecular structure, harmonic vibrational frequencies, energies and oscillator strengths for electronic transitions in order to validate the accuracy of approaches rooted into density functional theory with emphasis also on hybrid QM/QM′ models. Within the time-independent approaches, IR spectra are computed including anharmonicities through perturbative corrections while UV-vis line-shapes are simulated accounting for the vibrational structure; in both cases, the environmental effects are described by continuum models. The effects of conformational flexibility, including solvent dynamics, are described through time-dependent models based on purposely DFT-tailored force fields applied to molecular dynamics simulations and on QM computations of spectroscopic properties. Such procedures are exploited to simulate IR and UV-vis spectra of pyrimidine in the gas phase and in solutions, leading in all cases to good agreement with experimental observations and allowing to dissect different effects underlying spectral phenomena. [ABSTRACT FROM AUTHOR]

• The conformational space of spermidine3+ molecule is classified in 7 main conformational modes. • The bending of spermidine3+ is mainly facilitated by four of the seven dihedral angles in the backbone of the polyamine molecule. • Interaction of spermidine3+ with DNA induces highly bend conformations of the polyamine molecule. • Binding of spermidine3+ to the DNA macromolecule causes conformational changes of the double helix. Natural polyamines play a key role in many biological processes, particularly in the stabilization of DNA double helix structure in the cell nucleus. Among others, the conformational flexibility of polyamines, such as spermidine, is an essential property for the formation of complexes with DNA. Yet, the characterization of the conformational space of polyamines has not been fully elucidated. Using atomistic molecular dynamics (MD) simulations, we present a detailed study of the conformational space of spermidine3+ both in solution and in interaction with DNA. We have identified more than 2000 distinct conformations, which can be grouped into seven modes. Notably, the relative population of these modes is highly affected by the interaction of spermidine3+ with DNA, thus representing a fingerprint of complex formation. In particular, three of the seven dihedral angles of spermidine3+ are predominantly in trans conformation (with or without DNA), while the other four dihedral angles are observed to switch between trans , gauche + and gauche -. The preference between the latter conformational states was analyzed in terms of the distinct energy contributions composing the potential energy. Overall, our results shed light on the conformational equilibrium and dynamics of spermidine3+, which in turn is important for understanding the nature of its interaction with DNA. [ABSTRACT FROM AUTHOR]

Fluorescent probes are widely employed to label lipids for the investigation of structural and dynamic properties of model and cell membranes through optical microscopy techniques. Although the effect of tagging a lipid with an organic dye is generally assumed to be negligible, optically modified lipids can nonetheless affect the local lipid structure and, in turn, the lipid lateral mobility. To better assess this potential issue, all-atom (MD) molecular dynamics simulations have been performed to study structural and dynamic effects in a model DOPC membrane in the presence of a standard Rhodamine B-labeled DOPE lipid (RHB) as a function of temperature, i.e., 293 K, 303 K, and 320 K. As the temperature is increased, we observe similar changes in the structural properties of both pure DOPC and RHB-DOPC lipid bilayers: an increase of the area per lipid, a reduction of the membrane thickness and a decrease of lipid order parameters. The partial density profile of the RHB headgroups and their orientation within the lipid bilayer confirm the amphiphilic nature of the RHB fluorescent moiety, which mainly partitions in the DOPC glycerol backbone region at each temperature. Moreover, at all temperatures, our results on lipid lateral diffusion support a non-neutral role of the dye with respect to the unlabeled lipid mobility, thus suggesting important implications for optical microscopy studies of lipid membranes. [ABSTRACT FROM AUTHOR]

The recognition of quinolinic carboxylic acids as natural chelants and the recent observation of a high production of 8-hydroxyquinoline-2-carboxylic acid (8-HQA) in the gut of several Noctuid larvae (e.g. Spodoptera littoralis) has inspired the study of the chelation properties of 8-HQA towards Fe2+ and Fe3+. Here, we report a detailed characterization of the thermodynamic solution behaviour of Fe2+/8-HQA and Fe3+/8-HQA systems as a function of the pH value. The acid–base properties of 8-HQA and its binding ability towards Fe2+ and Fe3+ have been investigated over a wide range of pH values (2.0 ≤ pH ≤ 11.0) by ISE-H+ (glass electrode) potentiometric titrations in KCl(aq) at I = 0.2 mol dm−3 and at T = 298.15 K. For both oxidation states, various FeLqHr species are formed, with q = 1, 2 (and 3), and −2 ≤r≤ 1. The presence of the main FeLqHr species was confirmed by HESI-HRMS. ESR measurements have also been performed to get some extra information on the Fe3+ coordination, indicating a distorted octahedral symmetry around the metal center. Quantum mechanical calculations have been carried out in order to characterize the structural features of selected metal complexes. The complexing ability of 8-HQA is generally much higher for Fe3+ than Fe2+. Nevertheless, the sequestering ability of 8-HQA towards these two oxidation states of this metal ion, obtained by the calculation of several pL0.5 values, resulted in it being highly dependent on the pH value: (i) at relatively low pH values, it is higher for Fe3+ (pL0.5 = 6.3 at pH = 3.0) than for Fe2+ (pL0.5 = 3.1 at pH = 3.0); (ii) it is almost the same at pH = 8.1 (Fe3+: pL0.5 = 8.3; Fe2+: pL0.5 = 8.1); (iii) it is higher for Fe2+ at high pH values (pL0.5 = 8.9 for Fe2+ and pL0.5 = 6.2 for Fe3+ at pH = 10.0). The determination of the stability constants of the Fe2+/8-HQA and Fe3+/8-HQA complexes was also complemented by data obtained by the ligand-competition approach, using EDTA as a competing ligand over a wide range of cation and ligand concentrations and ratios. This also allowed a more thorough investigation of both the Fe2+/EDTA and Fe3+/EDTA systems, providing an accurate stability constant dataset for the Fep(EDTA)qHr species under the above-mentioned experimental conditions, which are commonly used in biological studies. [ABSTRACT FROM AUTHOR]

ABSTRACT The vapochromic properties of a fluorescent 3-[2-(4-nitrophenyl) ethenyl]-1-(2-ethylhexyl)-2-methylindole (NPEMI-E) characterized by intramolecular charge transfer (ICT) character, dispersed in polycarbonate (PC) films is reported. NPEMI-E solvatochromism is investigated by means of experimental and computational methods. Fluorescent PC films containing 0.1 wt % of NPEMI-E are prepared and exposed to saturated atmospheres of different volatile organic compounds (VOCs). NPEMI-E/PC films show remarkable and reversible vapochromism when exposed to VOCs with high polarity index and favorable interaction with PC matrix such as CHCl3. Only minor variations in the emission wavelength are actually recorded for all other classes of VOCs investigated. The hue parameter is also used for the effective extraction of spectral information from digital color images without the need for wavelength discriminators. Overall, the present results support the use of NPEMI-E/PC films for the cost-effective detection of CHCl3 vapors. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 1171-1180 [ABSTRACT FROM AUTHOR]

Background The bacterial proteins IscS, IscU and CyaY, the bacterial orthologue of frataxin, play an essential role in the biological machine that assembles the prosthetic Fe S cluster groups on proteins. They form functionally binary and ternary complexes both in vivo and in vitro. Yet, the mechanism by which they work remains unclear. Methods We carried out extensive molecular dynamics simulations to understand the nature of their interactions and the role of dynamics starting from the crystal structure of a IscS-IscU complex and the experimentally-based model of a ternary IscS-IscU-CyaY complex and used nuclear magnetic resonance to experimentally test the interface. Results We show that, while being firmly anchored to IscS, IscU has a pivotal motion around the interface. Our results also describe how the catalytic loop of IscS can flip conformation to allow Fe S cluster assembly. This motion is hampered in the ternary complex explaining its inhibitory properties in cluster formation. Conclusions We conclude that the observed ‘fluid’ IscS-IscU interface provides the binary complex with a functional adaptability exploited in partner recognition and unravels the molecular determinants of the reported inhibitory action of CyaY in the IscS-IscU-CyaY complex explained in terms of the hampering effect on specific IscU-IscS movements. General significance Our study provides the first mechanistic basis to explain how the IscS-IscU complex selects its binding partners and supports the inhibitory role of CyaY in the ternary complex. [ABSTRACT FROM AUTHOR]

Ferritin molecular cages are marvelous 24-mer supramolecular architectures that enable massive iron storage (>2000 iron atoms) within their inner cavity. This cavity is connected to the outer environment by two channels at C3 and C4 symmetry axes of the assembly. Ferritins can also be exploited as carriers for in vivo imaging and therapeutic applications, owing to their capability to effectively protect synthetic non-endogenous agents within the cage cavity and deliver them to targeted tissue cells without stimulating adverse immune responses. Recently, X-ray crystal structures of Fe2+-loaded ferritins provided important information on the pathways followed by iron ions toward the ferritin cavity and the catalytic centers within the protein. However, the specific mechanisms enabling Fe2+ uptake through wild-type and mutant ferritin channels is largely unknown. To shed light on this question, we report extensive molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements that characterize the transport properties and translocation mechanism of Fe2+ through the two ferritin channels, using the wild-type bullfrog Rana catesbeiana H' protein and some of its variants as case studies. We describe the structural features that determine Fe2+ translocation with atomistic detail, and we propose a putative mechanism for Fe2+ transport through the channel at the C3 symmetry axis, which is the only iron-permeable channel in vertebrate ferritins. Our findings have important implications for understanding how ion permeation occurs, and further how it may be controlled via purposely engineered channels for novel biomedical applications based on ferritin. [ABSTRACT FROM AUTHOR]

In recent years, engineered biological pores responsive to external stimuli have been fruitfully used for various biotechnological applications. Moreover, the strategy of tethering photo-switchable moieties into biomolecules has provided an unprecedented temporal control of purposely designed nanodevices, as demonstrated, for example, by the light-mediated regulation of the activity of enzymes and biochannels. Inspired by these advancements, we propose here a de novo designed nanodevice featuring the α-hemolysin (αHL) membrane channel purposely functionalized by an artificial “on/off” molecular switch. The switch, which is based on the photo-isomerization of the azobenzene moiety, introduces a smart nano-valve into the natural non-gated pore to confer tunable transport properties. We validated through molecular dynamics simulations and free energy calculations the effective inter-conversion of the engineered αHL pore between two configurations corresponding to an “open” and a “closed” form. The reported switchable translocation of a single-stranded DNA fragment under applied voltage supports the promising capabilities of this nanopore prototype in view of molecular sensing, detection and delivery applications at single-molecule level. [ABSTRACT FROM AUTHOR]

Watersolvation has a central role in several biochemical processes rangingfrom protein folding to biomolecular recognition and enzyme catalysis.Because of its importance, the structure and dynamics of hydrationlayers around biological macromolecules have been the targets of agreat number of experimental and computational studies. In the presentcontribution, we have investigated the effects of periodic boundaryconditions (PBCs), as used in conjunction with molecular dynamics(MD) simulations, on the dynamic and electric properties of waterlayers. In particular, we have systematically performed MD simulationsof neat water and biomolecules in aqueous solutions by imposing adifferent external dielectric constant, a generally overlooked parameterin PBC simulations. The effect of the system size has also been addressed.Overall, our results consistently indicate that the dipole momentproperties of water layers, and specifically the dipole moment fluctuationsand the reorientational correlation functions, can be sensitive tothe choice of the external boundary conditions, whereas other molecularproperties, such as the self-diffusion coefficient and the reorientationalrelaxation times, are not affected. We think that our investigationmay help to assess appropriate simulation conditions for modelingthe aqueous environment of relevant biochemical systems and processes. [ABSTRACT FROM AUTHOR]

The mechanosensitive channel of large conductance (MscL) is a protein that responds to membrane tension by opening a transient pore during osmotic downshock. Due to its large pore size and functional reconstitution into lipid membranes, MscL has been proposed as a promising artificial nanovalve suitable for biotechnological applications. For example, site-specific mutations and tailored chemical modifications have shown how MscL channel gating can be triggered in the absence of tension by introducing charged residues at the hydrophobic pore level. Recently, engineered MscL proteins responsive to stimuli like pH or light have been reported. Inspired by experiments, we present a thorough computational study aiming at describing, with atomistic detail, the artificial gating mechanism and the molecular transport properties of a light-actuated bacterial MscL channel, in which a charge-induced gating mechanism has been enabled through the selective cleavage of photo-sensitive alkylating agents. Properties such as structural transitions, pore dimension, ion flux and selectivity have been carefully analyzed. Besides, the effects of charge on alternative sites of the channel with respect to those already reported have been addressed. Overall, our results provide useful molecular insights into the structural events accompanying the engineered MscL channel gating and the interplay of electrostatic effects, channel opening and permeation properties. In addition, we describe how the experimentally observed ionic current in a single-subunit charged MscL mutant is obtained through a hydrophobicity breaking mechanism involving an asymmetric inter-subunit motion. [ABSTRACT FROM AUTHOR]

Fluorescent organic nanoparticles (FONs) based on aggregation-induced emission (AIE) are receiving increasing attention owing to their simple preparation, enhanced optical properties, and a wide range of applications. Therefore, finding simple methods to tune the structural and emissive properties of FONs is highly desirable. In this context, we discuss the preparation of highly emissive, amorphous AIE spherical nanoparticles based on a structurally-simple molecular rotor and their sono-chemical transformation into rhomboidal nanocrystals. Interestingly, the ultrasound-induced modification of the morphology is accompanied by a remarkable enhancement in the stability and emission of the resulting nanocrystals. Detailed characterization of both spherical and rhomboidal nanoparticles was carried out by means of several microscopic, crystallographic, and spectroscopic techniques as well as quantum mechanical calculations. In a nutshell, this work provides a unique example of the ultrasound-induced switching of morphology, stability, and emission in FONs. [ABSTRACT FROM AUTHOR]

The Azotobacter vinelandii rhodanese is a 31 kDa sulfurtransferase protein that catalyzes the transfer of sulfur atom from thiosulfate to cyanide in the detoxification process from cyanide and is able to insert sulfur atom in the iron–sulfur cluster. A study of the uniformly 15N isotopic labeling by high resolution NMR, before obtaining the backbone sequential assignment, has been carried out. The sulfur loaded and the sulfur discharged forms of the enzyme show very similar HSQC spectra with a good spectral dispersion. Few resonances show changes in chemical shift between the two forms. Relaxation parameters T1, T2 and 1H–15N NOE of all amide nitrogen atoms, as well as isotope exchange kinetics, show that the two forms exhibit the same global correlation time and hydrodynamic properties. In parallel, essential dynamics studies show that formation and discharging of catalytic cysteine persulfide group has no significant impact on the overall conformation of the protein. These results, taken together, give a clearcut answer to the question if the catalytic mechanism of the enzyme involves a change in the conformation and/or in the mutual orientation of the two domains. On the contrary these results clearly indicate that upon the catalytic mechanism the two domains of the protein behave as a unique fold. [Copyright &y& Elsevier]

We report on the synthesis and characterization of novel substituted 1,1′‐biperylene‐2,2′‐diols in which the dihedral angle between the two polycyclic aromatic hydrocarbon (PAH) units is tailored from ca. 60° to ca. 90° in the solid state by introduction of cyclo‐etheric straps or sterically hindered groups such as the triisopropylsilyl (TIPS) group. Depending on the type of substitution, we lock the dihedral angle between the perylenyl moieties enabling fine‐tuning of the molecular optoelectronic properties, with the molecules displaying the smallest angles acting as exceptionally strong emitters with unitary quantum yields. [ABSTRACT FROM AUTHOR]

Lipid lateral diffusion in membrane bilayers is a fundamental process exploited by cells to enable complex protein structural and dynamic reorganizations. For its importance, lipid mobility in both cellular and model bilayers has been extensively investigated in recent years, especially through the application of time-resolved, fluorescence-based, optical microscopy techniques. However, one caveat of fluorescence techniques is the need to use dye-labeled variants of the lipid of interest, thus potentially perturbing the structural and dynamic properties of the native species. Generally, the effect of the dye/tracer molecule is implicitly assumed to be negligible. Nevertheless, in view of the widespread use of optically modified lipids for studying lipid bilayer dynamics, it is highly desirable to well assess this point. Here, fluorescence correlation spectroscopy (FCS) and molecular dynamics (MD) simulations have been combined together to uncover subtle structural and dynamic effects in DOPC planar membranes enriched with a standard Rhodamine-labeled lipid. Our findings support a non-neutral role of the dye-labeled lipids in diffusion experiments, quantitatively estimating a decrease in lipid mobility of up to 20% with respect to the unlabeled species. Moreover, results highlight the existing interplay between dye concentration, lipid lateral diffusion and membrane permeability, thus suggesting possible implications for future optical microscopy studies of biophysical processes occurring at the membrane level. [ABSTRACT FROM AUTHOR]