Visualisation of variable binding pockets on protein surfaces by probabilistic analysis of related structure sets

Background: Protein structures provide a valuable resource for rational drug design. For a protein with no known ligand, computational tools can predict surface pockets that are of suitable size and shape to accommodate a complementary small-molecule drug. However, pocket prediction against single static structures may miss features of pockets that arise from proteins’ dynamic behaviour. In particular, ligand-binding conformations can be observed as transiently populated states of the apo protein, so it is possible to gain insight into ligand-bound forms by considering conformational variation in apo proteins. This variation can be explored by considering sets of related structures: computationally generated conformers, solution NMR ensembles, multiple crystal structures, homologues or homology models. It is non-trivial to compare pockets, either from different programs or across sets of structures. For a single structure, difficulties arise in defining particular pocket’s boundaries. For a set of conformationally distinct structures the challenge is how to make reasonable comparisons between them given that a perfect structural alignment is not possible. Results: We have developed a computational method, Provar, that provides a consistent representation of predicted binding pockets across sets of related protein structures. The outputs are probabilities that each atom or residue of the protein borders a predicted pocket. These probabilities can be readily visualised on a protein using existing molecular graphics software. We show how Provar simplifies comparison of the outputs of different pocket prediction algorithms, of pockets across multiple simulated conformations and between homologous structures. We demonstrate the benefits of use of multiple structures for protein-ligand and protein-protein interface analysis on a set of complexes and consider three case studies in detail: i) analysis of a kinase superfamily highlights the conserved occurrence of surface pockets at the active and regulatory sites ii) a simulated ensemble of unliganded Bcl2 structures reveals extensions of a known ligand-binding pocket not apparent in the apo crystal structure; iii) visualisations of interleukin-2 and its homologues highlight conserved pockets at the known receptor interfaces and regions whose conformation is known to change on inhibitor binding. Conclusions: Through post-processing of the output of a variety of pocket prediction software, Provar provides a flexible approach to the analysis and visualization of the persistence or variability of pockets in sets of related protein structures

Colloidal Cu 2-x(S ySe 1-y) alloy nanocrystals with controllable crystal phase: Synthesis, plasmonic properties, cation exchange and electrochemical lithiation

We report synthetic routes to both cubic and hexagonal phase Cu 2-x(S ySe 1-y) alloy nanocrystals exhibiting a well-defined near-infrared valence band plasmon resonance, the spectral position of which is dependent mainly on x, i.e. on Cu stoichiometry, and to a lesser extent on the crystal phase of the NCs. For cubic Cu 2-x(S ySe 1-y) nanocrystals y could be varied in the 0.4-0.6 range, while for hexagonal nanocrystals y could be varied in the 0.3-0.7 range. Furthermore, the Cu 2-x(S ySe 1-y) nanocrystals could be transformed into the corresponding Cd-based alloy nanocrystals with comparable S ySe 1-y stoichiometry, by cation exchange. The crystal phase of the resulting Cd(S ySe 1-y) nanocrystals was either cubic or hexagonal, depending on the phase of the starting nanocrystals. One sample of cubic Cu 2-x(S ySe 1-y) nanocrystals, with S 0.5Se 0.5 chalcogenide stoichiometry, was then evaluated as the anode material in Li-ion batteries. The nanocrystals were capable of undergoing lithiation/delithiation via a displacement/conversion reaction (Cu to Li and vice versa) in a partially reversible manner. © 2012 The Royal Society of Chemistry

Laser synthesis of ligand-free bimetallic nanoparticles for plasmonic applications.

A picosecond laser ablation approach has been developed for the synthesis of ligand-free AuAg bimetallic NPs where the relative amount of Ag is controlled in situ through a laser shielding effect. Various measurements, such as optical spectroscopy, transmission electron microscopy combined with energy dispersive X-ray spectroscopy and inductively coupled plasma optical emission spectrometry, revealed the generation of homogenous 15 nm average size bimetallic NPs with different compositions and tunable localized surface plasmon resonance. Furthermore, ligand-free metallic nanoparticles with respect to chemically synthesized nanoparticles display outstanding properties, i.e. featureless Raman background spectrum, which is a basic requirement in many plasmonic applications such as Surface Enhanced Raman Spectroscopy. Various molecules were chemisorbed on the nanoparticle and SERS investigations were carried out, by varying the laser wavelength. The SERS enhancement factor for AuAg bimetallic NPs shows an enhancement factor of about 5.7 × 105 with respect to the flat AuAg surface

Operando SAXS/WAXS on the a-P/C as the Anode for Na-Ion Batteries

A complete chemical and morphological analysis of the evolution of battery electrode materials can be achieved combining different and complementary techniques. Operando small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS) were combined to investigate structural and electrochemical performances of an Na-ion battery, with amorphous red phosphorus in a carbon matrix (a-P/C) as the active anode material in a Swagelok-type cell. The charging process results in the formation of crystalline Na3P, while during discharging, the anode material returns to the initial a-P/C. From the analysis of the WAXS curves, the formation of crystalline phases appears only at the end of charging. However, SAXS data show that partial reorganization of the material during charging occurs at length scales nonaccessible with conventional X-ray diffraction, corresponding to a real space ordering distance of 4.6 nm. Furthermore, the analysis of the SAXS data shows that the electrode remains dense during charging, while it develops some porosity during the discharge phase. The presented results indicate that the combination of SAXS/WAXS adopted simultaneously, and nondestructively, on a working electrochemical cell can highlight new mechanisms of reactions otherwise undetected. This method can be applied for the study of any other solid electrode material for batteries

Independent audit in Brazil: evolution from 1997 to 2008 and factors that can influence the auditeds choice for an auditor

As informações contábeis são de grande importância para o equilíbrio do relacionamento entre os stakeholders, sendo direcionadoras para a alocação de seus recursos. A auditoria independente, nesse contexto, surge como um importante mecanismo que contribui para proporcionar confiabilidade a essas informações, reduzindo o conflito de agência inerente a esse relacionamento, ao expressar uma opinião sobre a adequação das demonstrações contábeis às praticas de contabilidade. Diversas são as empresas de auditoria independente cadastradas na Comissão de Valores Mobiliários para realizar tais trabalhos no Brasil; no entanto, quatro empresas se destacam nesse rol: PriceWaterhouseCoopers, Deloitte Touche Tohmatsu, KPMG e Ernst & Young. Essas quatro empresas são mundialmente conhecidas como Big Four. Até 2001, tal grupo era denominado Big Five e tinha como integrante a Arthur Andersen, que deixou de atuar no ramo a partir de 2002. Este trabalho buscou verificar a participação dessas empresas no Brasil no período de 1997 a 2008. Para tanto, as empresas auditadas foram classificadas pelo ramo de atividade, controle acionário e negociação em bolsa de valores, a fim de verificar a participação das empresas de auditoria sob diferentes aspectos. A amostra foi composta de 2.024 empresas constantes do banco de dados da FIPECAFI no período contemplado na pesquisa. Os resultados apontam que, na média do período, aproximadamente 80% dos ativos das grandes empresas atuantes no Brasil são auditados por empresas do grupo Big Four. Em 2008 a líder geral no Brasil foi a KPMG, responsável por auditar mais de 30% dos ativos da amostra. Outro objetivo deste trabalho foi detectar características das empresas auditadas que poderiam ser indicadores para a empresa escolher um auditor componente do grupo das maiores empresas de auditoria independente, focando-se na influência dos credores nessa decisão. Para esse objetivo foram coletados dados contábeis das empresas auditadas, além das informações não contábeis já utilizadas na primeira análise de participação das auditadas (ramo de atividade, controle acionário e negociação em bolsa de valores) e aplicado o teste estatístico de regressão logística. Os resultados não mostraram que a situação econômica e financeira da auditada influencia essa escolha, mas apontaram para a importância do controle acionário e do porte da auditada.Accounting information have great importance for the balance of the relationship among stakeholders, and driving to the allocation of its resources. The independent audit, in this context, emerged as an important mechanism that helps to provide reliability of this information, reducing the agency conflict inherent in that relationship, to express an opinion on the adequacy of financial statements to accounting practices. There are several independent auditing firms registered at the Securities Commission to carry out such works in Brazil, however, four companies stand out in this list: PricewaterhouseCoopers, Deloitte Touche Tohmatsu, KPMG and Ernst & Young. These four companies are worldwide known as \"Big Four\". Until 2001, this group was called \"Big Five\" and had as a member Arthur Andersen, which no longer operate in the sector since 2002. This study aimed to verify their participation in Brazil from 1997 to 2008. For this, the audited companies were classified by line of business, stock control and trading on stock exchanges in order to assess the role of audit firms under different aspects. The sample consisted of 2024 companies listed in the database FIPECAFI the period covered in the survey. The results show that the average period of approximately 80% of the assets of large companies operating in Brazil are audited by firms of the group \"Big Four\". In 2008 the overall leader in Brazil was KPMG, responsible for auditing more than 30% of assets in the sample. Another objective was to identify characteristics of the audited companies that could be indicators for the company to choose an auditor of the component group of the largest independent audit, focusing on the influence of creditors in that decision. For this purpose, data were collected from accounting firms audited in addition to the information which were already used in the prior market share analysis (line of business, ownership control and stock trading on stock exchanges) and applied logistic regression statistical test. The results have shown that the economic and financial situation do not have any influence in that choice, but pointed the importance of ownership control and audited firms size in that choice

Hegemonia em declínio? : as relações entre EUA e China

t: Not informed Resumo: O objetivo deste trabalho é apresentar a atual condição sob a qual se encontra o ciclo hegemônico norte-americano e apontar as relações e contradições deste país com a China. A ideia central é apontar que os Estados Unidos vêm adotando estratégias diplomáticas equivocadas, o que tem criado oportunidades para a ascensão de outras nações, em especial a China. Além disso, serão analisados brevemente os ciclos hegemônicos observados até então, o que servirá de base para todo o estud

Determination of the parameters of quality of powder detergents using near infrared spectroscopy

Orientador: Celio PasquiniDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de QuimicaResumo: Este trabalho visa o desenvolvimento de um método analítico para a determinação dos parâmetros de qualidade em detergentes em pó utilizando a Espectroscopia de Infravermelho Próximo (NIR) e técnicas de calibração multivariada. Foram utilizados dois conjuntos de amostras: o primeiro para as análises quantitativas e o segundo para análises qualitativas. As amostras do primeiro conjunto tiveram os parâmetros de qualidade determinados pelos respectivos métodos de referência. A técnica estatística utilizada para as calibrações foi o PLS. Foram desenvolvidos modelos de calibrações para a previsão do teor de umidade, matéria ativa e densidade. O desempenho dos modelos de calibrações foi avaliado por meio de validação externa. A determinação do teor de umidade apresentou RMSEP = 0,29% (m/m). O valor de RMSEP para a determinação da matéria ativa foi de 0,37% (m/m) e para a determinação da densidade o valor de RMSEP = 14 g L . Os modelos construídos apresentaram resultados satisfatórios e os erros encontrados são aceitáveis para a faixa de controle utilizada na indústria. O segundo conjunto é composto de 4 grupos, que apresentam características distintas. Foram avaliados dois métodos de classificação: SIMCA e PLS DA. É possível observar que ocorre a discriminação das amostras que apresentam teor de matéria ativa mais elevado, no entanto, os outros grupos não puderam ser discriminados. Os dois métodos de classificação avaliados apresentaram resultados semelhantes, com acerto de 100% na classificação de amostras externas somente em seus respectivos gruposAbstract: This work aims the development of an analytical method for the determination of quality parameters on powder detergents using the near infrared spectroscopy (NIR) and multivariate calibration techniques. Two sets of samples were used: the first one for the quantitative analysis and the second one for qualitative analysis. The samples of the first set had the quality parameters determined by their respective methods of reference. The chemometric technique used for calibration was the PLS1. Calibrations for the prediction of de moisture content, active matter and density were developed. The performance of the calibration models was evaluated through external validation. The determination of the moisture content presented a RMSEP = 0,29% (w/w). The value of RMSEP for the determination of the active matter was 0,37% (w/w) and for the determination of moisture the value of RMSEP was 14 g L. The constructed models presented satisfactory results and the errors that were found are acceptable for the control range used in industry. The second set is composed of four groups of power detergents which present different characteristics. Two methods of classification were evaluated: SIMCA and PLS DA. It was possible to observe the discrimination of the samples which presents higher active matter content. However, the other groups could not be discriminated. Both methods of classifications evaluated presented similar results, with 100% correcte results of the classification of samples only in their respective groupsMestradoQuimica AnaliticaMestre em Químic