Le Rice yellow mottle virus (RYMV) est un virus émergeant qui constitue actuellement une contrainte majeure à la riziculture sur le continent africain. Quelques rares variétés de riz, issues des espèces cultivées de riz africain et asiatique (respectivement Oryza glaberrima et O. sativa), ont récemment été identifiées comme hautement résistantes au RYMV. Ce phénotype de résistance est dû à un gène récessif RYMV1 codant le facteur d'initiation de la traduction eIF(iso)4G1 du riz.Les objectifs de cette thèse sont (i) d'étudier la durabilité de la résistance élevée du riz contre le RYMV avant son déploiement à large échelle, (ii) de caractériser les mécanismes d'émergence de génotypes contournants et (iii) d'identifier des signatures moléculaires influençant ces processus d'adaptation. Ainsi, le contournement de deux allèles de résistance, identifiés chez les deux espèces de riz cultivés, a été relié à l'émergence de mutations dans la protéine virale VPg qui permettent de rétablir l'interaction avec le facteur eIF(iso)4G1 de l'hôte résistant. Un site sous sélection diversificatrice de la VPg influence directement la capacité de contournement de la résistance élevée en fonction de l'espèce hôte. Ce site, proche des mutations de contournement, est impliqué dans l'adaptation du virus à l'espèce O. glaberrima au cours de son histoire évolutive. La démarche employée au cours de ce travail combine des études d'évolution expérimentale à des analyses fonctionnelles. Les résultats obtenus par cette approche intégrative participeront à la mise en place de stratégies de lutte intégrée à la fois efficaces et durables face à la maladie de la panachure jaune du riz en Afrique. / The Rice yellow mottle virus (RYMV) is an emerging virus currently considered as the major constraint to rice production in Africa. Some varieties of African and Asian cultivated rice (Oryza glaberrima and O. sativa, respectively), have recently been identified as highly resistant to RYMV. This resistance phenotype is caused by a recessive gene RYMV1 encoding the translation initiation factor eIF(iso)4G1 of rice.The objectives of this thesis are (i) to investigate the durability of the high resistance of rice against RYMV before broadly deployment in fields, (ii) to characterize the mechanisms of emergence of resistance-breaking (RB) genotypes and (iii) to identify molecular signatures that influence these processes of adaptation. The resistance-breaking of two resistance alleles, identified in both cultivated rice species, is mainly associated with the emergence of mutations in the viral protein VPg that restore in resistant hosts the interaction with the factor eIF(iso)4G1. A site of VPg under diversifying selection directly affects the ability to overcome the high resistance depending on the host species. This site, near the RB mutations, is involved in the adaptation of the RYMV to O. glaberrima species during its evolutionary history. The approach used during this work combines experimental evolution and functional analyses. The results of this integrative study will participate in the development of effective and sustainable control strategies toward the Rice yellow mottle virus in Africa.

This volume provides a comprehensive introduction to the theory of electronic motion in molecular processes an increasingly relevant and rapidly expanding segment of molecular quantum dynamics. Emphasis is placed on describing and interpreting transitions between electronic states in molecules as they occur typically in cases of reactive scattering between molecules, photoexcitation or nonadiabatic coupling between electronic and nuclear degrees of freedom. Electron Dynamics in Molecular Interactions aims at a synoptic presentation of some very recent theoretical efforts to solve the electronic problem in quantum molecular dynamics, contrasting them with more traditional schemes. The presented models are derived from their roots in basic quantum theory, their interrelations are discussed, and their characteristic applications to concrete chemical systems are outlined. This volume also includes an assessment of the present status of electron dynamics and a report on novel developments to meet the current challenges in the field. Further, this monograph responds to a need for a systematic comparative treatise on nonadiabatic theories of quantum molecular dynamics, which are of considerably higher complexity than the more traditional adiabatic approaches and are steadily gaining in importance. This volume addresses a broad readership ranging from physics or chemistry graduate students to specialists in the field of theoretical quantum dynamics. / https://dc.etsu.edu/etsu_books/1055/thumbnail.jpg

Lors de la mise au point de biocapteurs, le contrôle de l'état de surface sur laquelle sontimmobilisées les biomolécules est un paramètre crucial pour la fiabilité et la reproductibilité desmesures. Pour ce travail de Thèse, deux objectifs principaux ont été fixés :- obtenir de façon reproductible des films organiques fonctionnels capables de rendre lessurfaces inorganiques biocompatibles afin d'immobiliser des biomolécules sans les dénaturer.- se doter d'outils innovants afin d'analyser la distribution de biomolécules sur la surface etd'évaluer leur activité biologique à l'échelle de la molécule unique.L'immobilisation a été réalisée sur des SAMs terminées par une fonction acide carboxylique.Pour imager les surfaces nous avons choisi la Microscopie Atomique de Force (AFM) qui permetd'obtenir des informations à l'échelle nanométrique et de mesurer des interactions moléculaires del'ordre du piconewton (10-12 N).Des CNTs, générés par dépôt chimique en phase vapeur, sont fixés sur une pointe AFM. Puis Ilssont biofonctionnalisés selon un protocole de trempage original afin d'obtenir une modificationchimique sélective de leur apex. Les interactions entre un récepteur, immobilisé sur la surface, et sonligand, lié de façon covalente au CNT, sont mesurées à l'échelle de la molécule unique. / During the development of biosensors, control of the surface on which the biomolecules areimmobilized is a crucial parameter for the reliability and reproducibility of the measurements. For thisPhD work, two main objectives were set:- obtain in a reproducible way functional organic films able to make inorganic surfacebiocompatible for the immobilization of biomolecules without any denaturation.- develop innovative tools in order to analyze the distribution of biomolecules on the surface etevaluate their biological activity at single molecule scaleThe immobilization step was done on SAMs terminated by a carboxylic acid function.In order to image surfaces, Atomic Force Microscopy (AFM) was chosen. This technique permits toobtain information at nanometric scale and to measure molecular interactions in the range ofpiconewton forces (10-12 N).MWCNTs were linked to a commercial AFM tip by micro-welding under optical microscopy. CNTswere biofunctionalized at the nanotube apex by an original dipping procedure.The interactions between a ligand, immobilized on the surface, and a receptor covalently linked to aCNT have been characterized.

A novel concept for protein recognition has been developed. The recognition unit is a hybrid molecule obtained by conjugation of a small organic molecule to a synthetic polypeptide selected from a 16-membered set of 42 amino acid residue sequences. The sequences are unordered and have no prior relation to the target proteins. The concept is based on the hypothesis that a small set of sequences capable of hydrophobic interactions, hydrogen bonding and electrostatic interactions can yield a binder for any selected protein, provided that the small molecule shows medium affinity or better and is reasonably selective. The concept has been illustrated by the design, synthesis and evaluation of binders for three different proteins, the C-reactive protein, CRP, human Carbonic anhydrase II, HCAII, and Acetylcholine esterase, AChE. Highly efficient binders for CRP have been developed by conjugation of a derivative of the natural ligand, phosphocholine, to the side chain of one of the amino acids in each polypeptide. The binders in the set show a wide range of affinities for CRP and the tightest binder, 4-C10L17-PC6, binds almost irreversibly. Selected binders have been evaluated in human serum, where they capture CRP with high selectivity.High-affinity binders have been developed for HCAII, and the selectivity evaluated by extraction of the protein from blood. The binder 4-C37L34-B, a polypeptide conjugated to a spacered benzenesulphonamide residue, was able to extract Carbonic anhydrases specifically and to discriminate between the two isoforms of human Carbonic anhydrase. The conjugation of an acridine derivative to a polypeptide via a 14 atom spacer has been shown to yield a binder with high affinity and selectivity for AChE. The selectivity was demonstrated by extraction of AChE from Cerebrospinal fluid. This thesis focuses on the development of a fast and reliable procedure for the construction, selection and evaluation of protein binders, with the ambition to develop a technology that is applicable to the development of binders for all proteins.

The work described in this thesis involves the study of weak interactions by NMR spectroscopy and using them to develop novel applications. The two different applications chosen are i) using molecular interactions for chiral discrimination and ii) understanding the nature of the interaction between peptide and nanoparticles to develop potent antibacterial agents. The thesis, which is divided into five chapters starts with a general introduction of NMR spectroscopy for the study of molecular interactions in conjunction with other techniques. The remaining four chapters focus on four different areas/projects that I have worked on. Chapter 1: Introduction This chapter reviews different kinds of molecular interactions along with the introduction to NMR spectroscopy and other techniques used for all the studies. Starting with the application of chiral discrimination the chapter proceeds to the general introduction of antimicrobial peptides, silver nanoparticles and the strategy for peptide resonance assignment. Chapter 2: Chiral discrimination for versatile functionalities There are many chiral agents available for discriminating enantiomers which mainly target specific functional groups. In this study, we have explored a strategy involving ternary complexation to investigate chiral discrimination of different kind of functional groups by NMR spectroscopy. The proposed protocol was employed for the enantiodiscrimination of molecules containing functional groups, such as amino alcohols, secondary alcohols, cyanohydrins, oxazolidones, diols, thiones and epoxides, using a phosphorous based three component mixture. The simple mixing and shaking of enantiopure 1,1’-binaphthyl-2,2’-diyl hydrogenphosphate (BNPA), 4-(dimethylamino)pyridine (DMAP) and a chiral analyte in the solvent CDCl3 served as a chiral solvating agent and resulted in well-dispersed peaks for each enantiomer in the 1H NMR spectrum. Discrimination was achieved not only for the proton at the chiral center but also for multiple proton sites. The J-resolved technique was used for alleviating the spectral complexity pattern to accurately measure the chemical shift difference. The devised approach also permitted the precise measurement of the enantiomeric excess (ee). Chapter 3: Simultaneous discrimination of secondary alcohols and carboxylic acids In this chapter, I describe two novel ternary ion-pair complexes, which serve as chiral solvating agents (CSA), for enantio discrimination of secondary alcohols and carboxylic acids. The superiority of CSA over other auxiliaries arises due to the formation of diastereomeric complexes through non-covalent interactions with the analyte. By exploiting the acid-base interaction strategy and employing DMAP, which further enhanced the hydrogen bonding efficiency the discrimination for both carboxylic acids and secondary alcohols were achieved. The protocol for discrimination of secondary alcohols is designed by using one equivalent mixture each of enantiopure mandelic acid, 4-dimethylaminopyridine (DMAP) and a chiral alcohol. For discrimination of carboxylic acids, the ternary complex is obtained by one equivalent mixture each of enantiopure chiral alcohol, DMAP, and a carboxylic acid. Furthermore, the formation of the complex was supported by calculating the energy-minimized structure of the proposed complex by density functional theory (DFT). The designed protocols also permit accurate measurement of the enantiomeric composition. Chapter 4: Enhanced potency of nanoparticle-antimicrobial peptide conjugates Antibiotic resistance is emerging as the new global health problem. Due to the blatant misuse and overuse of these drugs has resulted in the bacteria becoming resistant to a wide range of antibiotics. Researchers have found an alternative of current antibiotics which are a group of peptides known as antimicrobial peptides (AMP). But using these molecules as drug is rather costly due to high synthesis cost. Further the antibacterial activity of silver nanoparticle is well established. However, due to its toxic nature after, it cannot be used in high concentration. The conjugation of nanoparticles with antimicrobial peptides is emerging as a promising route to achieve superior anti-microbial activity. However, the nature of peptide-nanoparticle interactions in these systems remains unclear. This study describes the interactions of antimicrobial peptide with silver nanoparticles by NMR spectroscopy in conjunction with other biophysical techniques to completely understand the underlying mechanism of interaction between nanoparticles and peptide. It reveals that the conjugation process involves dynamic interaction between the nanoparticle and the peptide. This study also confirms the enhanced antibacterial efficiency of the nano-conjugate towards bacterial killing compared to the nanoparticle or the peptide alone. Chapter 5: Mechanistic insights into the action of nano-conjugates It is well established that antimicrobial peptides act as pore-formers to rupture the bacterial cells. This chapter is focused on studying the mechanism of action of the nano-conjugate with bacterial membrane mimic models. This study for the first time reveals the details of nanoconjugate membrane interaction at an atomic level. The pore formation mechanism and the enhanced efficiency of the nanoconjugate were explored using fluorescence spectroscopy, CD spectroscopy, and NMR spectroscopy. Structural changes of the peptide and the nanoparticle bound peptide have been captured which infers the propensity of the peptide to form a helical structure upon interacting with the membrane. The calculated structure of the peptide and nanoparticle bound peptide remains almost identical in presence of the membrane mimic environment. In the case of the nanoconjugate, the increase in local positive charge concentration makes the system to penetrate the bacterial membrane faster which further allows the nanoparticle to access the intercellular organelles easily. This dual mode of mechanism thus makes this nano-conjugate a promising antibacterial agent towards multi drug resistant bacteria. In summary, the thesis has focused on the studies of weak intermolecular interactions in different chemical and biological systems using NMR spectroscopy. It is demonstrated that in certain chemical systems, such interactions can be exploited to discriminate enantiomers and determine the enantiopurity of compounds by NMR. In the case of biomolecules, such weak interactions exist when protein or peptides interact with nanoparticles. Using silver nanoparticles, it is shown that such interactions result in a stable conjugate system. NMR spectroscopy provides valuable insights into the structure and dynamics of the system. Further, by using anti-microbial peptides conjugated with silver nanoparticles, new superior antibacterial agents can be developed.

<p>U prvom delu rada ispitana je adsorpcija četiri grupe organskih&nbsp;jedinjenja: (1) nitroaromatičnih (nitrobenzen), (2) nepolarno alifatičnih&nbsp;(heksan), (3)&nbsp; monoaromatičnih (benzen, toluen, 1,2,3- i 1,2,4-trihlorbenzen) i (4) policikličnih aromatičnih ugljovodonika, PAH&nbsp;(naftalen, fenantren, piren i fluoranten) na vi&scaron;eslojnim ugljeničnim&nbsp;nanocevima (od eng. multiwalled carbon nanotubes, MWCNTs). Cilj&nbsp;ovog dela rada bio je pronaći korelaciju između parametara adsorpcije i&nbsp;fizičko-hemijskih karakteristika organskih molekula, kao i parametara&nbsp;<br />adsorpcije i karakteristika adsorbenata. Na osnovu dobijenih korelacija&nbsp;predložiti mehanizam adsorpcije ispitivanih organskih molekula na&nbsp;MWCNT-u.</p><p>U cilju ispitivanja uticaja kiseoničnih funkcionalnih grupa na povr&scaron;ini&nbsp;MWCNT-a odabrane su tri vrste MWCNT-a: originalni, nemodifikovani&nbsp;MWCNT (OMWCNT) i dve vrste funkcionalno modifikovanog&nbsp;MWCNT-a koji su dobijeni tretiranjem sa kiselinom tokom 3 h&nbsp;(FMWCNT3h) i 6 h (FMWCNT6h). Sve adsorpcione izoterme opisane&nbsp;<br />su Freundlich-ovim modelom. Nelinearnost izotermi bila je u opsegu od&nbsp;0,418 do 0,897. Rezultati pokazuju da dobijeni afiniteti adsorpcije (za ravnotežnu koncentraciju 50% rastvorljivosti jedinjenja u vodi, K_d0,5 S_W) za PAH-ove rastu sa povećanjem specifične povr&scaron;ine (SP) adsorbenta. Veći afiniteti adsorpcije dobijeni su za velike molekule kao &scaron;to su PAH-ovi u poređenju sa malim molekulima (benzen, toluen i heksan) &scaron;to može biti posledica veće kontaktne povr&scaron;ine između većih molekula i povr&scaron;ine adsorbenta. Pozitivna korelacija između afiniteta adsorpcije i hidrofobnosti molekula ukazuje da hidrofobne interakcije dominantno kontroli&scaron;u adsorpciju ispitivanih organskih jedinjenja, osim u slučaju nitobenzena. Da bi se ispitao uticaj &pi;-&pi; interakcija,&nbsp; K_d za odabranu ravnotežnu koncentraciju su normalizovane sa hidrofobno&scaron;ću molekula pri čemu su dobijeni odgovarajući&nbsp; K_d/K_OW&nbsp;odnosi. Za sva ispitivana jedinjenja K_d/K_OW<font size="1">&nbsp;</font>odnosi na svim ispitivanim MWCNT rastu u sledećem nizu: nepolarni alifatični &lt; monoaromatični &lt; PAH-ovi &lt; nitrobenzen, &scaron;to ukazuje da &pi;-&pi; interakcije značajno pobolj&scaron;avaju adsorpciju aromatičnih jedinjenja na MWCNT-u. Snažne interakcije između MWCNT-a i nitrobenzena posledica su formiranja &pi;-&pi; elektron donorsko-akceptorskih (EDA) interakcija izemđu nitroaromatičnih molekula (elektron akceptori)i visoko polarizovane ugljenične povr&scaron;ine nanocevi (elektron donori). Na osnovu dobijenih rezultata može se uočiti da se pri adsorpciji ispitivanihorganskih molekula na MWCNT-u istovreme odigrava vi&scaron;e mehanizama.</p><p>U drugom delu rada ispitan je uticaj ugljeničnog nanomaterijala (od eng.&nbsp;carbon based nanomaterial, CNM) natransport odabranih organskih&nbsp;jedinjenja (1,2,3- i 1,2,4-trihlorbenzena, naftalena, fenantrena, pirena i&nbsp;fluorantena) kroz sediment Dunava. Cilj ovog dela rada bio je ispitati&nbsp;mehanizam transporta odabranih organskih jedinjenja u prisustvu i&nbsp;odsustvu CNM. C/C_0&nbsp;vrednosti, dobijene za vreme trajanja eksperimenta&nbsp;<br />(t=96 h), ispitivanog jedinjenja u eluatu kolone napunjene samo&nbsp;sedimentom rastu u sledećem nizu: fluoranten &lt; piren &lt; fenantren &lt;&nbsp;1,2,4-trihlorbenzen &lt; 1,2,3-trihlorbenzen &lt; naftalen. U cilju ispitivanja&nbsp;uticaja hidrofobnosti ispitivanih molekula na sorpciju u neravnotežnim&nbsp;uslovima, dobijene vrednosti C/C₀ ispitivanih molekula su korelirane sa&nbsp;hidrofobno&scaron;ću molekula. Uočena je negativna korelacija &scaron;to ukazuje da&nbsp;hidrofobniji molekuli pokazuju duže vreme zadržavanja na koloni, a time&nbsp;i veću neravnotežnu sorpcijutokom transporta.&nbsp;</p><p>U prisustvu FMWCNT3h u koloni kojaje napunjena sedimentom može&nbsp;se uočiti da su koncentracije ispitivanih jedinjenja u eluatu manje za 2-3&nbsp;puta. Pri datim uslovima procenat detektovane koncentracije ispitivanog&nbsp;jedinjenja u eluatu raste u sledećem nizu: fluoranten &lt; fenantren &lt; piren &lt; naftalen &lt; 1,2,4-trihlorbenzena &lt; 1,2,3-trihlorbenzen. Predloženi mehanizam je sledeći: na eksperimentalnoj pH (pH=6,5) karboksilne grupe na FMWCNT3h su negativno naelekrisane, s druge strane tačka nultog naelektrisanja sedimenta Dunav je 4, &scaron;to ukazuje da je ukupna povr&scaron;ina pri pH=6,5 negativno naelektrisana. Međutim, metalni oksidi i hidroksidi gvožđa, aluminijuma i nikla na povr&scaron;ini sedimenta uzrokuju pozitivno naelektrisane centre &scaron;to dovodi do depozicije FMWCNT3h kao posledica elektrostatičkog privlačenja. Pri transportu organskih jedinjenja kroz sediment Dunava u prisustvu FMWCNT3h dolazi do simultane sorpcije organskih jedinjenja na organskom ugljeniku sedimenta i do adsorpcije na FMWCNT3h. Kada se pH vrednost poveća smanjuje se pozitivno naelekrisanje metalnih&nbsp; oksida i hidroksida na povr&scaron;ini sedimenta &scaron;to dovodi do povećane mobilnosti FMWCNT3h, a time i organskih jedinjenja adsorbovanih na njima. Svi rezultati ukazuju da pH vrednost ima veoma značajnu ulogu i može povećati &nbsp;transport funkcionalizovanog MWCNT-a, a time i transport organskih molekula adsorbovanih na njima.</p> / <p>The first part of the thesis investigates the adsorption of four&nbsp;groups of organic compounds (OCs): (1) nitroaromatics (nitrobenzene),&nbsp;(2) nonpolar aliphatics (hexane), (3) monoaromatics (benzene, toluene,&nbsp;1,2,3- and 1,2,4-trichlorobenzene) and (4) polycyclic aromatic&nbsp;hydrocarbons (PAHs, napthalene,&nbsp; phenanthrene, pyrene and&nbsp;fluoranthene) on multiwalled carbon nanotubes (MWCNTs). This part of&nbsp;the work aimed to find a correlationbetween the adsorption parameters&nbsp;and physical-chemical properties of the organic molecules, as well as the&nbsp;parameters of adsorption and the characteristics of the adsorbents. On the&nbsp;basis of the obtained correlations the adsorption mechanism was&nbsp;proposed. In order to investigate the influence which oxygen containing&nbsp;functional groups exert on the adsorption process, three MWCNTs were&nbsp;used: the pristine (original, as-received) MWCNTs (OMWCNT) and two&nbsp;<br />MWCNTs functionally modified by acid treatment of OMWCNT over 3&nbsp;h and 6 h (FMWCNT3h, FMWCNT6h). All adsorption isotherms well&nbsp;fitted with the Freundlich model. The nonlinearity of the isotherms&nbsp;ranged from 0.418 to 0.897. The results show that K_d&nbsp;values for PAHs&nbsp;increased with increasing specific surface areas (SSAs). The adsorption&nbsp;affinities of the larger molecular size OCs (PAHs) were higher &nbsp;than those of the smaller size OCs (benzene, toluene and hexane) which is probably due to their large contact area with the surface of the adsorbent. Adsorption of OCs on MWCNTs was mainly controlled by hydrophobic interactions, except for the nitroaromatic compound, as shown by the increasing adsorption affinities with the compound&rsquo;s hydrophobicity. K_OW-normalized adsorption coefficients (K_d/K_OW) for all the investigated compounds on all the MWCNTs followed the order: nonpolar aliphatic &lt; monoaromatics &lt; PAHs &lt; nitroaromatic, implying that &pi;-&pi; interactions enhanced the adsorption of aromatics on the MWCNTs. It can be concluded that the strong adsorptiveinteractions between the MWCNTs and nitroaromatics was due to the &pi;-&pi; electron-donor&ndash;acceptor (EDA) interaction between nitroaromatic molecules (electron acceptors) and the highly polarisable graphene sheets(electron donors) of the carbon nanotubes. Based on the obtained results, it can be concluded that multiple mechanisms control the adsorption of organic compounds on MWCNTs.</p><p>In the second part, the influence of carbon based nanomaterials CNM on&nbsp;transport of selected organic compounds (1,2,3 - and 1,2,4-trichlorobenzene, naphthalene, phenanthrene, pyrene and fluoranthene)&nbsp;through sediment Danube was investigated. &nbsp;The aim of this part of the&nbsp;work was to investigate the transport mechanism of selected organic&nbsp;compounds in the presence and absence of CNM. The C/C_0&nbsp;values for the&nbsp;tested compounds in the eluate of the column filled with sediment only&nbsp;increased in the following order: fluoranthene &lt;pyrene &lt;phenanthrene&nbsp;&lt;1,2,4-trichlorobenzene &lt;1,2,3-trichlorobenzene &lt;naphthalene. In order&nbsp;to investigate the influence of&nbsp; hydrophobicity of the investigated&nbsp;compounds on the nonequilibrium sorption, the obtained C/C_0&nbsp;values (for&nbsp;the duration of the experiment, t = 96 h) for these molecules were&nbsp;correlated with the hydrophobicity of the molecules. There was a&nbsp;negative correlation, indicating that more hydrophobic molecules show&nbsp;long residence times in the column, and thus had higher non-equilibrium&nbsp;sorption during transport. In the presence of FMWCNT3h in the column&nbsp;filled with sediment, it can be observed that the concentrations of&nbsp;compounds in the column eluate decreased by factors of 2-3. C/C_0&nbsp;values&nbsp;for the investigated compounds in the eluate increased in the following&nbsp;order: fluoranthene &lt;phenanthrene &lt;pyrene &lt;naphthalene &lt;1,2,4-trichlorobenzene &lt;1,2,3-trichlorobenzene. The proposed mechanism is as&nbsp;follows: under the experimental pH (pH = 6.5), carboxyl groups are&nbsp;negatively charged on the surface of FMWCNT3h and the point of zero&nbsp;charge of the Danube sediment is 4, which indicates thatthe total surface of the Danube sediment at pH 6.5 isnegatively charged. However, metal oxides and hydroxides of iron, aluminum and nickel on the surface of the sediment cause a positively charged centre that leads to the deposition of FMWCNT3h as a result of electrostatic attraction. Transport of organic compounds through the Danube sediment in the presence FMWCNT3h leads to the simultaneous &nbsp;sorption oforganic compounds on the sediment organic carbon and the adsorption of &nbsp;FMWCNT3h. When the pH increased, the positive charge of metal oxides and hydroxides on the sediment surface decreased, which leads to increased FMWCNT3h mobility and thus the organic compounds adsorbed on them. All results indicate that the pH value plays animportant role and can increase the transport of functionally modified MWCNT&#39;s, and thus the transport of organic molecules adsorbed on them.&nbsp;</p>

L’un des obstacles majeurs à l’éradication du VIH-1 est sa capacité à faire évoluer rapidement son matériel génétique. Ceci lui permet de contourner le système immunitaire de l’hôte ainsi que la pharmacologie antirétrovirale due à l’émergence de formes mutantes et résistantes des enzymes ciblées. A l’origine de ses recombinaisons génétiques, se trouvent d'une part les erreurs commises par la RT lors de l’étape de transcription inverse et d'autre part les processus de transfert de brins qui sont facilités par la protéine de nucléocapside (NC). Notre objectif est de mieux comprendre les propriétés chaperon de la NC pendant le premier transfert de brin ; au cours de celui-ci, la NC déstabilise les structures secondaires des acides nucléiques impliqués ARN et ADN afin de les hybrider pour former un duplex ARN/ADN. Nous souhaitons notamment savoir si la NC est capable de reconnaître la polarité des chaines d’acides nucléiques selon leur nature et si cette capacité module ses propriétés déstabilisatrices. Nos travaux sur la dynamique interne de la protéine ont permis de montrer que certains mouvements étaient corrélés avec les modalités de fixation sur l’ARN. Nous avons ainsi pu montrer, en comparant les propriétés des différentes formes maturées de la NC au cours du cycle viral, que les domaines p1 et p6 présents dans les formes immatures (NCp9 et NCp15) modulaient les propriétés d’interaction comparé à la forme mature (NCp7). Ceci nous amène à reconsidérer le rôle des différentes parties de la polyprotéine Gag sur les propriétés du domaine NC au sein de ce précurseur Gag. Ce domaine apparaissant largement responsable de la reconnaissance et de la sélection du génome viral ARN pour l’encapsidation dans les particules néosynthétisées. Pour réaliser cette étude, nous avons étudié différents complexes entre la NC avec différents acides nucléiques (ARN et ADN), ce en utilisant principalement la résonance magnétique nucléaire couplée à d’autres méthodes biophysiques et biochimiques dans le but d’obtenir des informations à l’échelle atomique. Ce travail peut également être utile dans la conception d’une nouvelle classe d’inhibiteurs dirigés contre la NC sachant que celle-ci représente une cible thérapeutique attrayante vu qu’elle est très conservée et très importante pour l’infectiosité. / One of the major difficulty in the eradication of HIV-1 is its ability to evolve rapidly its genome. This permit to the virus to escape the host immune response and the antiretroviral pharmacology due to the emergence of mutant and resistant forms of the target enzymes.The origin of these genetic recombination is, in one hand the errors commited by the RT during the reverse transcription stage and in the other hand the strand transfer processes facilitated by the nucleocapsid protein (NC).Our goal is to understand the chaperonnig properties of NC protein during the first strand transfer ; where NC destabilizes the involved RNA and DNA secondary structures to anneal them and form a hybrid RNA/DNA duplex.In order to determine this mecanism, we seek, if NC protein have the property to recognize the polarity of nucleic acids chains and if this modulates its destabilization properties. Also, our work on the internal dynamic of the protein showed that some motions are correlated to its binding to RNA.We compared the properties of different maturated forms of NC protein during the viral life cycle and we concluded that p1 and p6 domains present within the immature forms (NCp9 and NCp15) adjusted differently the interaction properties to nucleic acids compared to the mature form (NCp7). It leads us to reconsider the role of the different parts of the Gag polyprotein on the properties of the NC domain within this Gag precursor. This domain appears to be largely responsible for the recognition and selection of the viral genomic RNA in order to package it in the newly formed viral particles.To permform this study, we studied different complexes between NC and nucleic acids sequences (RNA and DNA) using mainly NMR spectroscopy and biophysical or biochemical methods to obtain informations at the atomic scale. This work can also be useful in the design of a new class of inhibitors against NC protein which is an attractive therapeutic target due to its conservation and importance in viral infectivity.

Protein electrical properties have been studied using dielectric relaxation measurements throughout the past century. These measurements have advanced both the theory and practice of liquid dielectric spectroscopy and have contributed to understanding of protein structure and function. In this dissertation, the relationship between permittivity measurements and underlying molecular mechanisms is explored. Also presented is a method to take molecular structures from the Protein Data Bank and subsequently estimate the charge distribution and dielectric relaxation properties of the proteins in solution. This process enables screening of target compounds for analysis by dielectric spectroscopy as well as better interpretation of protein relaxation data. For charge estimation, the shifted pKa values for amino acid residues are calculated using Poisson-Boltzmann solutions of the protein electrostatics over varying pH conditions. The estimated internal permittivity and estimated dipole moments through shifted pKa values are then calculated. Molecular dynamics simulations are additionally used to refine and approximate the solution-state conformation of the proteins. These calculations and simulations are verified with laboratory experiments over a large pH and frequency range (40 Hz to 110 MHz). The measurement apparatus is improved over previous designs by controlling temperature and limiting the electrode polarization effect through electrode surface preparation and adjustment of the cell's physical dimensions. The techniques developed in this dissertation can be used to analyze a wide variety of molecular phenomena experimentally and computationally, as demonstrated through various interactions amongst avidin, biotin, biotin-labeled and unlabeled bovine serum albumin, beta-lactoglobulin, and hen-lysozyme.

There are puzzle pieces to the cure for Alzheimer’s Disease (AD), and such can emerge by inspecting the biomolecular interactions and their effects on neuronal cells. The upcoming presented literature review will cover the molecular changes caused by AD pathological progression, explore the relationship between non-AD molecules and AD molecules in the body, and analyze potential contributing factors in AD. In addition, the information to be provided will highlight medicinal alternatives respective to a particular stage in AD.

Microcantilever sensor has gained much popularity because of its high sensitivity and selectivity. It consists of a micro-sized cantilever that is usually coated on one side with chemical/biological probe agents to generate strong attraction to target molecules. The interactions between the probe and target molecules induce surface stress that bends the microcantilever. This current work applied the molecular dynamics simulation to study the microcantilever system. Lennard-Jones potentials were used to model the target-target and target-probe interactions and bond bending potentials to model the solid cantilever beam. In addition, this work studied the effect of probe locations on the microcantilever deflection. The simulation results suggest that both target-target and target-probe interactions as well as the probe locations affect the arrangement of the bonds; in term of the bonding number, the area containing the bonded molecules, and the distances between them. All these factors influence the microcantilever deflection.