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The electronic circular dichroism (ECD) spectra of aqueous d-glucose and d-galactose were modeled using a theoretical–computational approach combining molecular dynamics (MD) simulations and perturbed matrix method (PMM) calculations, hereafter termed MD-PMM. The experimental spectra were reproduced with a satisfactory accuracy, confirming the good performances of MD-PMM in modeling different spectral features in complex atomic–molecular systems, as already reported in previous studies. The underlying strategy of the method was to perform a preliminary long timescale MD simulation of the chromophore followed by the extraction of the relevant conformations through essential dynamics analysis. On this (limited) number of relevant conformations, the ECD spectrum was calculated via the PMM approach. This study showed that MD-PMM was able to reproduce the essential features of the ECD spectrum (i.e., the position, the intensity, and the shape of the bands) of d-glucose and d-galactose while avoiding the rather computationally expensive aspects, which were demonstrated to be important for the final outcome, such as (i) the use of a large number of chromophore conformations; (ii) the inclusion of quantum vibronic coupling; and (iii) the inclusion of explicit solvent molecules interacting with the chromophore atoms within the chromophore itself (e.g., via hydrogen bonds). [ABSTRACT FROM AUTHOR]

(1) Background: the theoretical modelling of reactions occurring in liquid phase is a research line of primary importance both in theoretical–computational chemistry and in the context of organic and biological chemistry. Here we present the modelling of the kinetics of the hydroxide-promoted hydrolysis of phosphoric diesters. (2) Method: the theoretical–computational procedure involves a hybrid quantum/classical approach based on the perturbed matrix method (PMM) in conjunction with molecular mechanics. (3) Results: the presented study reproduces the experimental data both in the rate constants and in the mechanistic aspects (C–O bond vs. O–P bond reactivity). The study suggests that the basic hydrolysis of phosphodiesters occurs through a concerted A N D N mechanism, with no formation of penta-coordinated species as reaction intermediates. (4) Conclusions: the presented approach, despite the approximations, is potentially applicable to a large number of bimolecular transformations in solution and therefore leads the way to a fast and general method to predict the rate constants and reactivities/selectivities in complex environments. [ABSTRACT FROM AUTHOR]

In this paper, we introduce specific approximations to simplify the vibronic treatment in modeling absorption and emission spectra, allowing us to include a huge number of vibronic transitions in the calculations. Implementation of such a simplified vibronic treatment within our general approach for modelling vibronic spectra, based on molecular dynamics simulations and the perturbed matrix method, provided a quantitative reproduction of the absorption and emission spectra of aqueous indole with higher accuracy than the one obtained when using the existing vibronic treatment. Such results, showing the reliability of the approximations employed, indicate that the proposed method can be a very efficient and accurate tool for computational spectroscopy. [ABSTRACT FROM AUTHOR]

A theoretical-computational procedure based on the quasi-Gaussian entropy (QGE) theory and molecular dynamics (MD) simulations is proposed for the calculation of thermodynamic properties for molecular and supra-molecular species in the gas phase. The peculiarity of the methodology reported in this study is its ability to construct an analytical model of all the most relevant thermodynamic properties, even within a wide temperature range, based on a practically automatic sampling of the entire conformational repertoire of highly flexible systems, thereby bypassing the need for an explicit search for all possible conformers/rotamers deemed relevant. In this respect, the reliability of the presented method mainly depends on the quality of the force field used in the MD simulations and on the ability to discriminate in a physically coherent way between semi-classical and quantum degrees of freedom. The method was tested on six model systems (n-butane, n-butane, n-octanol, octadecane, 1-butyl-3-methylimidazolium hexafluorophosphate and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic pairs), which, being experimentally characterized and already addressed by other theoretical-computational methods, were considered as particularly suitable to allow us to evaluate the method's accuracy and efficiency, bringing out advantages and possible drawbacks. The results demonstrate that such a physically coherent yet relatively simple method can represent a further valid computational tool that is alternative and complementary to other extremely efficient computational methods, as it is particularly suited for addressing the thermodynamics of gaseous systems with a high conformational complexity over a large range of temperature. [ABSTRACT FROM AUTHOR]

Here, we extend a recently introduced theoretical-computational procedure [M. D'Alessandro, M. Aschi, C. Mazzuca, A. Palleschi, and A. Amadei, J. Chem. Phys. 139, 114102 (2013)] to include quantum vibrational transitions in modelling electronic spectra of atomic molecular systems in condensed phase. The method is based on the combination of Molecular Dynamics simulations and quantum chemical calculations within the Perturbed Matrix Method approach. The main aim of the presented approach is to reproduce as much as possible the spectral line shape which results from a subtle combination of environmental and intrinsic (chromophore) mechanical-dynamical features. As a case study, we were able to model the low energy UV-vis transitions of pyrene in liquid acetonitrile in good agreement with the experimental data. [ABSTRACT FROM AUTHOR]

In a recent paper [Aschi et al., ChemPhysChem 6, 53 (2005)], we characterized, by means of theoretical-computational procedures, the electronic excitation of water along the typical liquid state isochore (55.32 mol/l) for a large range of temperature. In that paper we were able to accurately reproduce the experimental absorption maximum at room temperature and to provide a detailed description of the temperature dependence of the excitation spectrum along the isochore. In a recent experimental work by Marin et al. [J. Chem. Phys. 125, 104314 (2006)], water electronic excitation energy was carefully analyzed in a broad range of density and temperature, finding a remarkable agreement of the temperature behavior of the experimental data with our theoretical results. Here, by means of the same theoretical-computational procedures (molecular dynamics simulations and the perturbed matrix method), we investigate water electronic absorption exactly in the same density-temperature range used in the experimental work, hence, now considering also the absorption density dependence. Our results point out that, (1) for all the densities and temperatures investigated, our calculated absorption spectra are in very good agreement with the experimental ones and (2) the gradual maxima redshift observed increasing the temperature or decreasing the density has to be ascribed to a real shift of the lowest X→A electronic transition, supporting the conclusions of Marin et al. [ABSTRACT FROM AUTHOR]

In a recent paper [M. D’Alessandro, M. D’Abramo, G. Brancato, A. Di Nola, and A. Amadei, J. Phys. Chem. B 106, 11843 (2002)] we showed how to combine molecular dynamics simulations with the quasi-Gaussian entropy theory, in order to model the statistical mechanics and thermodynamics of ionic (water) solutions. In this paper we extend the method to treat nonspherical solutes, describe more thoroughly its theoretical basis and apply it to a set of more complex solute molecules in water (i.e., water, methane, ethane, methanol, and ethanol). Results show that this approach can really provide an excellent theoretical description of solute–solvent systems over a wide range of temperatures. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

In this article, we investigated the structural and dynamical evolutionary behaviour of a set of ten thioredoxin proteins as formed by three extant forms and seven resurrected ones in laboratory. Starting from the crystallographic structures, we performed all-atom molecular dynamics simulations and compare the trajectories in terms of structural and dynamical properties. Interestingly, the structural properties related to the protein density (i.e. the number of residues divided by the excluded molecular volume) well describe the protein evolutionary behaviour. Our results also suggest that the changes in sequence as occurred during the evolution have affected the protein essential motions, allowing us to discriminate between ancient and extant proteins in terms of their dynamical behaviour. Such results are yet more evident when the bacterial, archaeal and eukaryotic thioredoxins are separately analysed. [ABSTRACT FROM AUTHOR]

The UV–vis spectrum of Tyrosine and its response to different backbone protonation states have been studied by applying the Perturbed Matrix Method (PMM) in conjunction with molecular dynamics (MD) simulations. Herein, we theoretically reproduce the UV–vis absorption spectrum of aqueous solution of Tyrosine in its zwitterionic, anionic and cationic forms, as well as of aqua‐p‐Cresol (i.e., the moiety that constitutes the side chain portion of Tyrosine). To achieve a better accuracy in the MD sampling, the Tyrosine Force Field (FF) parameters were derived de novo via quantum mechanical calculations. The UV–vis absorption spectra are computed considering the occurring electronic transitions in the vertical approximation for each of the chromophore configurations sampled by the classical MD simulations, thus including the effects of the chromophore semiclassical structural fluctuations. Finally, the explicit treatment of the perturbing effect of the embedding environment permits to fully model the inhomogeneous bandwidth of the electronic spectra. Comparison between our theoretical–computational results and experimental data shows that the used model captures the essential features of the spectroscopic process, thus allowing to perform further analysis on the strict relationship between the quantum properties of the chromophore and the different embedding environments. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We present here the calculation of the absorption spectrum of riboflavin in acetonitrile and dimethyl sulfoxide using a hybrid quantum/classical approach, namely the perturbed matrix method, based on quantum mechanical calculations and molecular dynamics simulations. The calculated spectra are compared to the absorption spectrum of riboflavin previously calculated in water and to the experimental spectra obtained in all three solvents. The experimentally observed variations in the absorption spectra upon change of the solvent environment are well reproduced by the calculated spectra. In addition, the nature of the excited states of riboflavin interacting with different solvents is investigated, showing that environment effects determine a recombination of the gas-phase electronic states and that such a recombination is strongly affected by the polarity of the solvent inducing significant changes in the absorption spectra. [ABSTRACT FROM AUTHOR]

The understanding of the factors governing the enzyme catalysis is one of the most important goals of biochemistry and biophysics. In this context the contribution of theoretical research might be of high relevance. However, despite the huge amount of proposed approaches, the modelling of enzyme reactions still represents a very difficult task and a definitive and conclusive theoretical-computational strategy is still far from being available. In this study, after a presentation of the main difficulties associated to a coherent and possibly rigorous modelling of these processes, we present a computationaltheoretical method specifically designed for addressing complex molecular systems eventually applied to a benchmark reaction: the initial proton transfer in Triosephosphate Isomerase. This latter species, termed as the 'perfect enzyme' because of its exceptional ability as catalyst, provides an excellent test for evaluating the different environmental and intrinsic determinants at the basis of enzyme activity. [ABSTRACT FROM AUTHOR]

The theoretical modeling of chemical reactions in condensed phase still represents an open field of investigation for theoretical-computational chemistry. In this context, we have proposed a methodology (the Perturbed Matrix Method [PMM]), based on the first principles of statistical mechanics and on the use of molecular simulations, which has demonstrated its ability in quantitatively predicting the kinetics and the thermodynamics of chemical reactions in complex atomistic environments. In this study, we demonstrate the features of PMM by modeling the resonant Electron Transfer bimolecular reaction between ferrocene and ferrocenium in solution. The obtained results, despite the adopted approximations and the intrinsic limitations of the approach, are in very good agreement with the experimental data and demonstrate the ability of the method for addressing complex reactions in solution and for evaluating the kinetics of slow events out of the potentialities of the state-of-the-art molecular simulations. [ABSTRACT FROM AUTHOR]

The understanding of the factors governing the enzyme catalysis is one of the most important goals of biochemistry and biophysics. In this context the contribution of theoretical research might be of high relevance. However, despite the huge amount of proposed approaches, the modelling of enzyme reactions still represents a very difficult task and a definitive and conclusive theoretical-computational strategy is still far from being available. In this study, after a presentation of the main difficulties associated to a coherent and possibly rigorous modelling of these processes, we present a computational-theoretical method specifically designed for addressing complex molecular systems eventually applied to a benchmark reaction: the initial proton transfer in Triosephosphate Isomerase. This latter species, termed as the 'perfect enzyme' because of its exceptional ability as catalyst, provides an excellent test for evaluating the different environmental and intrinsic determinants at the basis of enzyme activity. [ABSTRACT FROM AUTHOR]

Essential Dynamics (ED) is a powerful tool for analyzing molecular dynamics (MD) simulations and it is widely adopted for conformational analysis of large molecular systems such as, for example, proteins and nucleic acids. In this study, we extend the use of ED to the study of clusters of arbitrary size constituted by weakly interacting particles, for example, atomic clusters and supramolecular systems. The key feature of the method we present is the identification of the relevant atomic-molecular clusters to be analyzed by ED for extracting the information of interest. The application of this computational approach allows a straightforward and unbiased conformational study of the local microstructures in liquids, as emerged from semiclassical MD simulations. The good performance of the method is demonstrated by calculating typical observables of liquid water, that is, NMR, NEXAFS O1s, and IR spectra, known to be rather sensitive both to the presence and to the conformational features of hydrogen-bonded clusters. [ABSTRACT FROM AUTHOR]

Dynamic protein-solvent interactions are fundamental for life processes, but their investigation is still experimentally very demanding. Molecular dynamics simulations up to hundreds of nanoseconds can bring to light unexpected events even for extensively studied biomolecules. This paper reports a combined computational/experimental approach that reveals the reversible opening of two distinct fluctuating cavities in Saccharomyces cerevisiae iso-1-cytochrome c. Both channels allow water access to the heme center. By means of a mixed quantum mechanics/molecular dynamics (QM/MD) theoretical approach, the perturbed matrix method (PMM), that allows to reach long simulation times, changes in the reduction potential of the heme Fe3+/Fe2+ couple induced by the opening of each cavity are calculated. Shifts of the reduction potential upon changes in the hydration of the heme propionates are observed. These variations are relatively small but significant and could therefore represent a tool developed by cytochrome c for the solvent driven, fine-tuning of its redox functionality. [ABSTRACT FROM AUTHOR]

Molecular-level structural information on amyloid aggregates is of great importance for the understanding of protein-misfolding-related deseases. Nevertheless, this kind of information is experimentally difficult to obtain. In this work, we used molecular dynamics (MD) simulations combined with a mixed quantum mechanics/molecular mechanics theoretical methodology, the perturbed matrix method (PMM), in order to study the amide I' IR spectrum of fibrils formed by a short peptide, the H1 peptide, derived from residues 109 through 122 of the Syrian hamster prion protein. The PMM/MD approach allows isolation of the amide I' signal arising from any desired peptide group of the polypeptide chain and quantification of the effect of the excitonic coupling on the frequency position. The calculated single-residue signals were found to be in good agreement with the experimental site-specific spectra obtained by means of isotope-labeled IR spectroscopy, providing a means for their interpretation at the molecular level. In particular, our results confirm the experimental hypothesis that residues ala117 are aligned in all strands and that the alignment gives rise to a red shift of the corresponding site-specific amide I' mode due to strong excitonic coupling among the ala117 peptide groups. In addition, our data show that a red shift of the amide I' band due to strong excitonic coupling can also occur for amino acids adjacent in sequence to the aligned ones. Thus, a red shift of the signal of a given isotope-labeled amino acid does not necessarily imply that the peptide groups under consideration are aligned in the β-sheet. [ABSTRACT FROM AUTHOR]

The mechanism of base catalyzed keto-enol interconversion of aqueous 2-phenylacetylthiophene has been investigated by a joint application of experimental and computational approaches. Primarily we have focused our attention on the water-enolate proton transfer representing the rate determining step of the reaction. Computational results, in good agreement with experimental data demonstrate the crucial role exerted by the solvent. In particular, beyond the bulk catalytic effect an explicit assistance of solvent molecules allows the reaction to increase its efficiency. A combination on Molecular Dynamics simulations and Perturbed Matrix Method calculations also highlight the subtle balance between energetic and entropic effects which characterize the mechanistic scenario. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [ABSTRACT FROM AUTHOR]

In this paper, we present an extension of the theoretical-computational methodology based on the perturbed matrix method and molecular dynamics simulations that we introduced in a recent paper (Daidone et al., Chem Phys Lett 488:213-218, ). This methodology models quantum vibrational states of polyatomic systems (i.e. beyond the one-dimensional vibrational mode case) embedded in a complex atomic-molecular environment such as liquid-state conditions. In the extended model, we now include the anharmonic correction to the excitation frequency of each mode and the excitonic coupling effects, providing a detailed description of the theoretical basis and an explicit scheme to achieve a very efficient implementation of the method. Application of the proposed procedure to study the amide I band of the infrared spectra of a β-hairpin peptide shows that a quantitative and accurate reproduction of the experimental spectral variations due to folding-unfolding transition can be achieved. [ABSTRACT FROM AUTHOR]

The state-of-the-art of theoretical-computational modelling of infrared (IR) spectra in peptides and proteins is able to reproduce the main spectral features involved in the secondary-structure organisation. The results so far collected, clearly show that the complexity of the atomic processes inherent to the IR spectra makes the often used empirical secondary-structure/frequency correlations inaccurate and possibly misleading. The use of extended configurational sampling as provided by, for example, molecular dynamics simulations and of a physically coherent treatment of both the quantum degrees of freedom and their coupling with the semiclassical atomic motions, promises to open the way to interpret and predict IR temperature-dependent and time-dependent spectral signals, in particular for the study of folding/unfolding transitions. [Copyright &y& Elsevier]

[Display omitted] • Electronic and magnetic properties of L-alanine in cationic form in water have been studied combining experimental measurements and theoretical-computational calculations. • The calculated Circular Dichroism spectrum well reproduces the corresponding experimental data. • The conformational effects, which are explicitly treated in our theoretical approach, determine the CD spectral behavior. • The absorption essential features, absorption maximum position and intensity, are in line with the experimental data. • Our approach can be easily extended to the modelling of the CD spectrum of more complex solutes. Here we present an advanced theoretical-computational approach to model the electronic circular dichroism (CD) spectrum of the smallest chiral amino acid in water solution. Combining quantum–mechanical calculations with molecular dynamics simulations the electronic and magnetic properties of L-alanine (L-Ala) in solution are obtained and compared with the corresponding experimental measurements in the same conditions. The calculation of the CD spectrum, in good agreement with the experimental data, revealed a remarkable dependence on the conformational behavior of the molecule in solution, which was properly treated by our approach. [ABSTRACT FROM AUTHOR]

Recent work has shown that the nature of hydration of pure hydrophobic surfaces changes with the length scale considered: water hydrogen-bonding networks adapt to small exposed hydrophobic species, hydrating or ‘wetting’ them at relatively high densities, whereas larger hydrophobic areas are ‘dewetted’ [Chandler D (2005), Nature 29:640-647]. Here we determine whether this effect is also present in peptides by examining the folding of a β-hairpin (the 14-residue amyloidogenic prion protein H1 peptide), using microsecond time-scale molecular dynamics simulations. Two simulation models are compared, one explicitly including the water molecules, which may thus adapt locally to peptide configurations, and the other using a popular continuum approximation, the generalized Born/surface area implicit solvent model. The results obtained show that, in explicit solvent, peptide conformers with high solvent-accessible hydrophobic surface area indeed also have low hydration density around hydrophobic residues, whereas a concomitant higher hydration density around hydrophilic residues is observed. This dewetting effect stabilizes the fully folded β-hairpin state found experimentally. In contrast, the implicit solvent model destabilizes the fully folded hairpin, tending to cluster hydrophobic residues regardless of the size of the exposed hydrophobic surface. Furthermore, the rate of the conformational transitions in the implicit solvent simulation is almost doubled with respect to that of the explicit solvent. The results suggest that dehydration-driven solvent exposure of hydrophobic surfaces may be a significant factor determining peptide conformational equilibria. [ABSTRACT FROM AUTHOR]

Abstract: In this Letter, we use the perturbed matrix method, in combination with molecular dynamics and statistical mechanics, in order to describe in details the electric field induced intramolecular charge transfer (ICT) in two π-conjugated oligomers of nanotechnological interest. Results show a relevant relationship between the extent of ICT and molecular conformation, pointing out the highly non-linear charge transfer field response. [Copyright &y& Elsevier]

The free energy profile and the (classical) kinetics of chemical reactions in (soft) condensed phase are modeled theoretically by means of molecular dynamics simulations, the Perturbed Matrix Method (PMM) and the quasi Gaussian entropy (QGE) theory. In this paper we describe the theoretical framework and apply the model to the intramolecular proton transfer reaction of aqueous malonaldehyde. Although in the present application we disregard the quantum effects for the proton dynamics along the reaction coordinate (i.e., tunneling), the classical-like view of the proton transition over the reaction free energy surface seems to properly describe the kinetic process and shows that water acts lowering the reaction free energy barrier. Moreover, a weak temperature dependence of the free energy surface is obtained, implying small entropy variations in the transition. Interestingly the activation entropy, as provided by the QGE model, is negative in the whole temperature range considered, thus indicating an entropy reduction at the transition structure. Finally, by comparing our results with theoretical and experimental literature data, we critically address the actual role of tunneling in this reaction and discuss the emerging kinetic scheme. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Due to its high quantum yield and long fluorescence lifetime, pyrene molecule is a widely used fluorescence probe. From a theoretical–computational viewpoint, the modeling of its emission properties in different environments still represents a challenge, mainly because the coupling with the environment severely affects its emission behavior. We employed our computational–theoretical approach to quantitatively model the pyrene emission, which combines quantum chemical calculations with all-atom molecular dynamics simulations. Our calculated fluorescence properties, well matching the experimental data, highlight that even slight geometrical fluctuations of pyrene at room temperature can provide relevant effects on its radiative lifetime. [ABSTRACT FROM AUTHOR]

Theamide I′ infrared spectrum of a α-helical photoswitchablepeptide is calculated here by means of a mixed quantum mechanics/moleculardynamics theoretical–computational methodology based on theperturbed matrix method (PMM). The contribution of specific residuesto the total spectrum is also analyzed and the results compared toprevious experimental spectroscopic data, obtained by means of site-specificisotope labeling at different residues, resulting in good agreement.One of the residues (Ala7) shows atypical spectroscopic behavior inboth the experimental and calculated spectra, i.e., the folded-stateamide I′ band is shifted to higher frequencies than the unfolded-stateone, while the other residues show the opposite behavior. The calculationsreveal the origin of this uncommon spectroscopic trend and point toa crucial role of the molecular switch, the presence of which perturbsthe conformational sampling of the peptide. Indeed, infrared spectraof the same peptide calculated in the absence of the molecular switchshow that the single-residue spectrum of Ala7 does not have any distinguishingfeature, resembling the spectra of the other analyzed residues. [ABSTRACT FROM AUTHOR]

Infrared spectroscopy has long provided a means to estimatethesecondary structure of proteins and peptides. In particular, the vibrationalspectra of the amide I′ band have been widely used for thispurpose as the frequency positions of the amide I′ bands arerelated to the presence of specific secondary structures. Here, wecalculate the amide I′ IR spectra of polylysine in aqueoussolution in its three secondary structure states, i.e., α-helix,β-sheet, and random coil, by means of a mixed quantum mechanics/moleculardynamics (QM/MD) theoretical–computational methodology basedon the perturbed matrix method (PMM). The computed spectra show agood agreement with the experimental ones. Although our calculationsconfirm the importance of the excitonic coupling in reproducing importantspectral features (e.g., the width of the absorption band), the frequencyshift due to secondary-structure changes is also well reproduced withoutthe inclusion of the excitonic coupling, pointing to a role playedby the local environment. Concerning the β-conformation spectrum,which is characterized by a double-peak amide I′ band due toexcitonic coupling, our results indicate that it does not correspondto a generic antiparallel β-sheet (e.g., of the typical sizepresent in native proteins) but is rather representative of extendedβ-structures, which are common in β-aggregates. Moreover,we also show that the solvent has a crucial role in the shape determinationof the β-conformation amide I′ band and in particularin the disappearance of the high-frequency secondary peak in the caseof small sheets (e.g., 6-stranded). [ABSTRACT FROM AUTHOR]

The self-association equilibria of doxorubicin hydrochloride (DX), at high drug and NaCl concentrations, are studied by temperature scan fluorescence spectroscopy, with the support of molecular dynamics (MD) calculations. Even though all anthracyclines show dimerization equilibria, DX only can further associate into long polymeric chains according to DX mon ⇄ DX dim ⇄ DX pol. This is reflected not only in the mechanical properties of DX pol solutions (behaving as thixotropic gels) but also in their spectroscopic behaviour. Fluorescence, in particular, is the technique of election to study this complex set of equilibria. Upon increasing the temperature, DX pol melts into DX dim , which in turn is in equilibrium with DX mon. Since DX dim is non fluorescent, with a fluorescence temperature scan experiment the DX pol ⇄ DX mon equilibrium is probed. However, also information on the DX dimerization equilibrium can be derived together with the relevant thermodynamic parameters ruling the dimerization process (Δ H d i m ° = - 56 k J m o l - 1 ; Δ S d i m ° = - 97 J m o l - 1 K - 1). The residence time of DX molecules in the dimer (74.7 μs), as well as the monomers mutual orientation in the dimer, are characterized by means of theoretical and computational modelling. [ABSTRACT FROM AUTHOR]

In this study we report the modeling of the absorption spectrum of riboflavin in water using a hybrid quantum/classical mechanical approach, the MD-PMM methodology. By means of MD-PMM calculations, with which the effect of riboflavin internal motions and of solvent interactions on the spectroscopic properties can be explicitly taken into account, we obtain an absorption spectrum in very good agreement with the experimental spectrum. In particular, the calculated peak maxima show a consistent improvement with respect to previous computational approaches. Moreover, the calculations show that the interaction with the environment may cause a relevant recombination of the gas-phase electronic states. [ABSTRACT FROM AUTHOR]

A theoretical-computational approach is presented to characterize the temperature-dependent thermodynamics of protein folding. Making use of the Quasi-Gaussian Entropy (QGE) theory and temperature exchanged molecular dynamics (TREMD) simulations, a complete picture of the folding thermodynamics can be obtained. The strategy is applied to analyze the folding thermodynamics of a β -hairpin peptide, Peptide 1, the folding process of which was experimentally characterized by means of infrared spectroscopy. The results provided by the approach here presented very well reproduce the experimental results, showing that the methodology can be successfully utilized to investigate the thermodynamics of folding processes in a wide temperature range. [ABSTRACT FROM AUTHOR]

Protein folding is one of the most fundamental problems in modern biochemistry. Time-resolved infrared (IR) spectroscopy in the amide I region is commonly used to monitor folding kinetics. However, associated atomic detail information on the folding mechanism requires simulations. In atomistic simulations structural order parameters are typically used to follow the folding process along the simulated trajectories. However, a rigorous test of the reliability of the mechanisms found in the simulations requires calculation of the time-dependent experimental observable, i.e., in the present case the IR signal in the amide I region. Here, we combine molecular dynamics simulation with a mixed quantum mechanics/molecular mechanics theoretical methodology, the Perturbed Matrix Method, in order to characterize the folding of a β-hairpin peptide, through modeling the time-dependence of the amide I IR signal. The kinetic and thermodynamic data (folding and unfolding rate constants, and equilibrium folded- and unfolded-state probabilities) obtained from the fit of the calculated signal are in good agreement with the available experimental data [Xu et al. J. Am. Chem. Soc. 2003, 125, 15388-15394]. To the best of our knowledge, this is the first report of the simulation of the time-resolved IR signal of a complex process occurring on a long (microsecond) time scale. [ABSTRACT FROM AUTHOR]

Graphical abstract: Ferrocene electronic spectra are calculated in solution with an original methodology. Results, in good agreement with experimental data, indicate that solvent nature does not heavily affect UV-spectra but is relevant for redox potential. Display Omitted Highlights: [•] The UV–Vis spectra of Ferrocene in different solvents have been calculated. [•] The Ferrocene/Ferricinium couple redox potential in the same solvents. [•] Change of the solvent only affect the redox potential. [ABSTRACT FROM AUTHOR]

Protein folding and unfolding under the effect of exogenousperturbationsremains a topic of great interest, further enhanced by recent technologicaldevelopments in the field of signal generation that allow the useof intense ultrashort electric pulses to directly interact at microscopiclevel with biological matter. In this paper, we show results frommolecular dynamics (MD) simulations of a single myoglobin moleculein water exposed to pulsed and static electric fields, ranging from108to 109V/m, compared to data with unexposedconditions. We have found that the highest intensity (109V/m) produced a fast transition (occurring within a few hundredsof picoseconds) between folded and unfolded states, as inferred bysecondary structures and geometrical analysis. Fields of 108V/m, on the contrary, produced no significant denaturation, althougha relevant effect on the protein dipolar behavior was detected. [ABSTRACT FROM AUTHOR]

Abstract: Firefly luciferin and its oxidated form, oxyluciferin, are two heterocyclic compounds involved in the enzymatic reaction, catalyzed by redox proteins called luciferases, which provides the bioluminescence in a wide group of arthropods. Whereas the electronic absorption spectra of d-luciferin in water at different pHs are known since 1960s, only recently reliable experimental electronic spectra of oxyluciferin have become available. In addition oxyluciferin is involved in a triple chemical equilibria (deprotonation of the two hydroxyl groups and keto-enol tautomerism of the 4-hydroxythiazole ring), that obligates to select during an experiment a predominant species, tuning pH or solvent polarity besides introducing chemical modifications. In this study we report the absorption spectra of luciferin and oxyluciferin in each principal chemical form, calculated by means of perturbed matrix method (PMM), which allowed us to successfully introduce the effect of the solvent on the spectroscopic absorption properties, and compare the result with available experimental data. [Copyright &y& Elsevier]

The free-energy profile and the classical kinetics of the heme carbomonoxide binding−unbinding reaction have been derived by means of a theoretical method for the separated chains of human (HbA) and Trematomus newnesi major component (HbTn) hemoglobin. The results reveal that the α- and β-chains of HbA have similar values of kinetic constants for the dissociation of the Fe−CO state, in agreement with experimental data. Comparisons of the present findings with the data obtained for the α- and β-chains of HbTn and with theoretical and experimental results previously collected on myoglobin provide a detailed picture of this important biochemical reaction in globins. The sequence and structural differences among the globins are not reflected in meaningful variations in the rate of CO dissociation. These data support the conclusion that the differences observed for the reaction with CO of globins, if any, involve the rate of ligand migration to the solvent, rather than the Fe−CO complex formation/rupture. Furthermore, our results agree with the recent discovery that globin family proteins exhibit common dynamics, thus confirming the observation that the dynamic properties of proteins are strongly related to their overall architecture. [ABSTRACT FROM AUTHOR]

Abstract: In this letter we use X-ray scattering data of liquid water, as obtained by different experimental and theoretical-computational procedures, to address the problem of quantitative modeling of the scattering signal in liquids. In particular we investigate the accuracy of well optimized water models in reproducing top level X-ray experimental results and compare experimental data variations with the ones given by different theoretical-computational models. Results show that the experimental scattering data have an intrinsic noise which is comparable to the deviations of the theoretical-computational signals, hence suggesting that no reliable refinement based on scattering data is possible for such models. [Copyright &y& Elsevier]

Abstract: In this work, we address the problem of the role and relevance of the aqueous environment configurational sampling on acetone electronic properties: the (vertical) absorption spectrum and corresponding excitation Helmholtz free energy. By comparing the results obtained by applying the perturbed matrix method (PMM) on molecular dynamics (MD) trajectories of different sampling efficiency, we specifically quantify the effects of the phase space sampling on acetone vertical electronic excitations. Results confirm that PMM provides an accurate and physically consistent description of the electronic excitation processes and show the crucial importance of an extended configurational sampling of the solvent environment in order to obtain a reliable (chromophore) absorption behaviour. [Copyright &y& Elsevier]

By means of the conformational free energy surface and corresponding diffusion coefficients, as obtained by long time scale atomistic molecular dynamics simulations (μs time scale), we model the folding kinetics of α-helix and β-hairpin peptides as a diffusive process over the free energy surface. The two model systems studied in this paper (the α-helical temporin L and the β-hairpin prion protein H1 peptide) exhibit a funnel-like almost barrierless free energy profile, leading to nonexponential folding kinetics matching rather well the available experimental data. Moreover, using the free energy profile provided by Muñoz et al. [Muñoz et al. Nature 1997, 390: 196-199], this model was also applied to reproduce the two-state folding kinetics of the C-terminal β-hairpin of protein GB1, yielding an exponential folding kinetics with a time constant (∼5 μs) in excellent agreement with the experimentally observed one (∼6 μs). Finally, the folding kinetics obtained by solving the diffusion equation, considering either a one-dimensional or a two-dimensional free energy surface, are also compared in order to understand the relevance of the possible kinetic coupling between conformational degrees of freedom in the folding process. [ABSTRACT FROM AUTHOR]

Abstract: By means of principle component analysis of the local density fluctuations, as revealed by molecular dynamics simulations, we obtain detailed information on the relevant local density fluxes and corresponding spatial patterns. [Copyright &y& Elsevier]