1,721,171 research outputs found
QM/MM study of bioluminescent systems
No full textLa bioluminescence est un processus complexe dans lequel la réaction chimique d'un substrat, catalysée par une protéine, entraîne l'apparition d'une émission de lumière dans le spectre visible. Dans le cas des lucioles, un insecte émettant dans le domaine du jaune-vert, le substrat se nomme luciférine et la protéine luciférase. Cependant, la taille et la complexité de ce système chimique limite sa compréhension, notamment celle du mécanisme réactionnel.L'apport de la chimie théorique dans ce domaine est essentiel et a prouvé son utilité dans de nombreux cas. L'utilisation de la méthode QM/MM, méthode hybride couplant la mécanique quantique et la mécanique moléculaire permet de modéliser et d'étudier ces systèmes biologiques.Cette thèse se focalise sur deux approches différentes de l'étude de la bioluminescence chez les lucioles. La première consiste à étudier l'effet de certaines modifications chimiques sur la couleur de la bioluminescence. On s'intéresse plus particulièrement à un analogue de la luciférine et à certaines luciférases issues d'autres systèmes bioluminescents. Par cette étude on cherche à rationaliser et à prédire l'effet ainsi que l’impact de ces changements sur l’émission. Le deuxième sujet explore deux étapes du mécanisme réactionnel de la bioluminescence: d'une part, la coordination du dioxygène sur un intermédiaire de la réaction, une étape encore non étudiée et d'autre part la réaction de tautomérisation dans l'état excité et au sein de la protéine entre deux formes émissives possibles de la luciférineThe bioluminescence is a complex process that involves the reaction of a substrate, catalysed by an enzyme that sheds light in the visible spectra. In fireflies, the light emitted has a yellow-green tone thanks to the interaction between the substrate luciferin and the protein luciferase. However the size and the complexity of the system prevent its comprehension especially when dealing with the reaction mechanism.The use of computational chemistry is key to understand and improve the comprehension of the bioluminescence. The hybrid QM/MM method that combines quantum mechanics with molecular mechanics is a great tool to model and study bioluminescent systems.This thesis deals with two different approaches of the bioluminescence in fireflies. The first one is related to the study of chemical modifications that tune the emission colour. We will discuss about one analogue of the luciferin and on new luciferases from others bioluminescent species. The goals of this study are to rationalise and predict both the effect and the impact of these modifications on the emission. The second subject deals with two different steps of the bioluminescent mechanism. The first one discusses the binding of the dioxygen to the bioluminescent intermediate, which was so far unstudied and the second one about the tautomerization in the excited state and in the protein of two possible emissive forms of the luciferi
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Caractérisation du départ du phosphate de la myosine VI par simulations de dynamique moléculaire
No full textLes myosines constituent une superfamille de protéines agissant comme moteur moléculaire au sein d'un cycle. Ce cycle est alimenté par l'hydrolyse de l'ATP comme source d'énergie, ce qui donne un ADP et un phosphate inorganique (Pi). Nous nous sommes intéressés au cycle de la myosine et particulièrement à l'étape concernant la production de force ainsi que sa relation au départ du phosphate. Nous proposons dans cette thèse d'étudier par des moyens de simulations de dynamique moléculaire la place du départ du phosphate dans le cycle de la myosine. Nous utilisons notamment une structure cristallographique d'un nouvel état de la myosine VI résolue en 2015 et nommée Pi-Release du fait que certaines de ses caractéristiques laissent penser que cet état permet le départ du phosphate. Notamment, cette structure présente une des principales portes de sorties du phosphate ouverte. Comme ce nouvel état de la protéine a son convertisseur qui est encore pratiquement complètement ”armé”, il constitue un élément en faveur d'un départ du phosphate avant le ”powerstroke”. Cependant des modèles basés sur des résultats d'études physiologiques tendent à décrire le départ du phosphate après le ”powerstroke” quand d'autres ne donnent aucun lien entre départ du phosphate et powerstroke. Ces modèles ne sont pas en accord avec un état Pi-Release avant le powerstroke. Pour cela nous avons comparé l'état Pi-Release par rapport à deux états de la myosine avant et après le début du powerstroke : les états Pre-powerstroke et Strong-ADP respectivement. Plusieurs méthodologies ont été développées pour effectuer cette comparaison. La caractérisation des trois états se base sur la comparaison des structures cristallographiques et celles issues de relaxations tout atome en l'absence de l'actine. Nous utilisons cette caractérisation pour essayer de transformer la myosine de l'état Pre-powerstroke à Strong-ADP afin de voir si l'on visitait l'état Pi-Release lors de la transition. Afin d'étudier spécifiquement le départ du Pi, nous avons effectué des simulations d'Umbrella Sampling en forçant le départ du Pi en partant de plusieurs structures relaxées de Pre-powerstroke et Pi-Release. Ces structures relaxées ont été choisies avec des orientations du Pi protoné différentes pour étudier l'influence de l'orientation du Pi sur son départ. De plus, des relaxations spécifiques de Pre-powerstroke et Pi-Release sans Pi ont été réalisées pour comprendre quel est l'impact de la présence du Pi dans le site actif. Cette thèse permet d'avoir des éléments pour mieux comprendre l'état Pi-Release de la myosine VI et comprendre le départ du PiMyosins are a superfamily of proteins acting as molecular motors. This motor activity takes place in a cycle fueled by ATP hydrolysis. The ATP hydrolysis produces an ADP and an inorganic phosphate Pi. We study the cycle of myosin, particularly the step of powerstroke, the force-generating step, and its relationship with Pi release.In this thesis we aim at studying by molecular dynamics simulations the place of Pi release in the myosin cycle. Our calculations use a crystallographic state of myosin VI solved in 2015 named Pi-Release because it exhibits characteristics favoring Pi departure. Notably, this state presents one of the main Pi exit door open.As this state also shows a mostly armed converter, it constitutes an argument in favor of Pi departure before the powerstroke. However, models based on results from physiological studies propose that the powerstroke precedes the departure of Pi while others would give no mandatory relative timing between Pi release and powerstroke. These models are incompatible with a Pi-Release state before the powerstroke. We have compared the Pi-Release state with two states prior and after the powerstroke, called Pre-Powerstroke and Strong-ADP respectively. Several methodologies were developed to perform the comparison of the states. The characterization of the three states is based on the comparison of crystallographic structures and snapshots from relaxation molecular dynamics without actin. We use the characterization of the states to try to transform the myosin from Pre-Powerstroke conformation to Strong-ADP and check whether the Pi-Release state is visited along the transition.In order to study specifically the departure of Pi, we performed Umbrella Sampling simulations forcing the departure of Pi. These simulations were started from relaxed structures in the Pre-Powerstroke and Pi-Release states. These relaxed structures were obtained at the end of relaxation started with different orientation of protonated Pi in order to study the impact of the orientation of Pi on its departure. Moreover, relaxation of Pre-Powerstroke and Pi-Release without Pi were realized to study the impact of the absence of Pi in the structure.This thesis gives some elements to better understand the Pi-Release state and the departure of P
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Mechanistic insights into chemiluminescent decomposition of firefly dioxetanone
No full textThe decomposition mechanism and pathway of the firefly dioxetanone have never been explored at a reliable theoretical level before. The difficulty is that the decomposition process includes biradical, charge-transfer (CT) and several nearly degen- erated states, which is in need of multireference method for considering several states simultaneously with an active space available to the whole reaction process. We have investigated the thermolysis of firefly dioxetanone in both neutral (FDOH) and anionic (FDOÀ) forms in gas phase and solvents by the mul- tistate second-order multiconfigurational perturbation (CASPT2) theories in coordination with the ground-state intrinsic reac- exchange-correlation (CAM-B3LYP). The size of selected active spaces have been validated adequate large for handing the whole reaction processes of the decompositions of FDOH and FDOÀ, together with the assistance of state-average (SA) tech- nique. The decomposition processes of FDOH and FDO- were explored in details. The activation energy of FDOÀ is 5.9 kcal/mol smaller than that of FDOH by the CASPT2 cal- culations, which once again indicates the necessary of depro- present calculations, the chemically initiated electron exchange luminescence (CIEEL) and charge-transfer initiated luminescence (CTIL) mechanisms were extremely discussed
QM/MM study of firefly bioluminescence
No full textInternational audienceThe emitting light in fireflies arises from the electronic relaxation of oxyluciferin, an organic compound resulting from the oxidation of the D-luciferin substrate inside an enzyme called luciferase. In order to theoretically study such systems, the use of quantum mechanical/molecular mechanical (QM/MM) methods is required. Accurate QM level is needed for dealing with electronic transition and charge transfer phenomena. Taking into account the surrounding protein at the MM level is essential in order to understand the colour modulation and influence of the enzyme.The present lecture will discuss some of the results obtained on this system with calculations done with the coupling of the programs MOLCAS (CASPT2/CASSCF) or G09 (DFT) and TINKER (AMBER force field) and how the complementary of experimental data and theoretical results can give understanding of such phenomenon.The transition energy corresponding to a fluorescence experiment for the wild type emitter and a modified emitter will be presented.Calculations give insights to decipher the emitter conformation even with a lack of experimental crystallographic structure. And insights to explain the color modulation due to the surrounding environment
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