1,215 research outputs found
Membrane-associated proteins and peptides
No full textThis chapter discusses the practical aspects of setting up molecular dynamics simulations for membrane-associated proteins and peptides. Special emphasis lies on the analysis of such systems. The main focus is the association between a cationic peptide and an anionic lipid bilayer-a peptide/lipid-bilayer system-but the extension onto more complicated systems is discussed. Topology files for selected lipids and several new analysis tools relevant for protein-membrane simulations are presented, the most important ones of which are: g-helixaxis, to calculate the axis of a helix and its angle with the bilayer; g-arom, to calculate aromatic order parameters; and g-under, to calculate which lipids interact with the protein. A procedure is explained to calculate properties involving peptide-interacting lipids only, as opposed to all lipids. © 2008 Humana Press.SCOPUS: ar.kinfo:eu-repo/semantics/publishe
Molecular Dynamics Simulation of the Effect of Hydrophobic Cosolutes on the Neutral Hydrolysis of an Activated Ester
No full textWe have studied, by means of molecular dynamics (MD) simulations, the effect of two hydrophobic cosolutes, tert-butanol (t-BuOH) and ethanol (EtOH), on the neutral hydrolysis of p-methoxyphenyl dichloroacetate (MPDA) in water. Shifts were calculated in a pre-equilibrium, defined as a spatial distribution of the reacting molecules satisfying specific geometric constraints. The criteria applied represent the configurations from which the reaction can take place (reactive conformation, RC). The shifts induced by the presence of cosolute, as determined from the simulations, correspond well to the experimentally found rate retardations. In accord with experiments, an almost linear correlation between the concentration of added cosolute and the logarithm of the rate constant was found. This is in agreement with a simple mechanistic model. The percentage of RCs in pure water was calculated to be ~15%, complementing earlier work performed in this group (Lensink, M. F.; Mavri, J.; Berendsen, H. J. C. J. Comput. Chem. 1999, 20, 886), leading to a calculated rate constant of kcalc = 3.9 × 10-3 s-1 (exptl: kobs ) 2.78 × 10-3 s-1). The molecular structure of the RC was examined more extensively, investigating correlations between the positions of participating molecules.
Metadata initiatives and emerging technologies to improve resource discovery
No full textThis paper discusses some emerging issues on metadata as a mechanism of resource discovery and its impact on precision of search results in a distributed network environment. It presents a brief account of the recent major developments related to metadata across the globe. Highlights a consistent growth of multiple metadata standards to meet the variety of needs in a hierarchy of complexity. Examines various metadata-harvesting tools and related technologies that fulfill the task implicit in a user’s search. Brings out popular standards, useful protocols, and open-source harvesters along with their intrinsic capabilities for harvesting and presenting metadata and introduces a variety of metadata services viz., OCLC’s catalogue service, UKOLN metadata editor service, OAIster harvester service, DP9 gateway service, etc. explores the underlying principles of metadata-harvesting in DSpace and web search engines. Discusses use of multiple metadata formats in DSpace archives for exposing domain-specific metadata; and the inherent mechanism for extensibility and interoperability functions. Proposes methods for creating metadata that can pursue high-precision document retrieval in dynamic collections. Also discuses semantic web technologies and use of specialized metadata for long-term management and preservation of digital objects
Erratum: An algorithm-based topographical biomaterials library to instruct cell fate (Proceedings of the National Academy of Sciences of the United States of America (2011) 108, 40 (16565-16570) DOI: 10.1073/pnas.1109861108)
No full textAPPLIED BIOLOGICAL SCIENCES Correction for “An algorithm-based topographical biomaterials library to instruct cell fate,” by Hemant V. Unadkat, Marc Hulsman, Kamiel Cornelissen, Bernke J. Papenburg, Roman K. Truckenmüller, Gerhard F. Post, Marc Uetz, Marcel J. T. Reinders, Dimitrios Stamatialis, Clemens A. van Blitterswijk, and Jan de Boer, which appeared in issue 40, October 4, 2011, of Proc Natl Acad Sci USA (108:16565–16570; first published September 26, 2011; 10.1073/pnas.1109861108). The authors note that Anne E. Carpenter and Matthias Wessling should be added to the author list between Roman K. Truckenmüller and Gerhard F. Post. Anne E. Carpenter should be credited with analyzing data. Matthias Wessling should be credited with designing research. The corrected author and affiliation lines, and author contributions appear below. The online version has been corrected
Introducing a clustering step in a consensus approach for the scoring of protein-protein docking models
No full textCorrectly scoring protein-protein docking models to single out native-like ones is an open challenge. It is also an object of assessment in CAPRI (Critical Assessment of PRedicted Interactions), the community-wide blind docking experiment. We introduced in the field the first pure consensus method, CONSRANK, which ranks models based on their ability to match the most conserved contacts in the ensemble they belong to. In CAPRI, scorers are asked to evaluate a set of available models and select the top ten ones, based on their own scoring approach. Scorers' performance is ranked based on the number of targets/interfaces for which they could provide at least one correct solution. In such terms, blind testing in CAPRI Round 30 (a joint prediction round with CASP11) has shown that critical cases for CONSRANK are represented by targets showing multiple interfaces or for which only a very small number of correct solutions are available. To address these challenging cases, CONSRANK has now been modified to include a contact-based clustering of the models as a preliminary step of the scoring process. We used an agglomerative hierarchical clustering based on the number of common inter-residue contacts within the models. Two criteria, with different thresholds, were explored in the cluster generation, setting either the number of common contacts or of total clusters. For each clustering approach, after selecting the top (most populated) ten clusters, CONSRANK was run on these clusters and the top-ranked model for each cluster was selected, in the limit of 10 models per target. We have applied our modified scoring approach, Clust-CONSRANK, to SCORE-SET, a set of CAPRI scoring models made recently available by CAPRI assessors, and to the subset of homodimeric targets in CAPRI Round 30 for which CONSRANK failed to include a correct solution within the ten selected models. Results show that, for the challenging cases, the clustering step typically enriches the ten top ranked models in native-like solutions. The best performing clustering approaches we tested indeed lead to more than double the number of cases for which at least one correct solution can be included within the top ten ranked models
Docking and scoring protein interactions: CAPRI 2009
No full textProtein docking algorithms are assessed by evaluating blind predictions performed during 2007-2009 in Rounds 13-19 of the community-wide experiment on critical assessment of predicted interactions (CAPRI). We evaluated the ability of these algorithms to sample docking poses and to single out specific association modes in 14 targets, representing 11 distinct protein complexes. These complexes play important biological roles in RNA maturation, G-protein signal processing, and enzyme inhibition and function. One target involved protein-RNA interactions not previously considered in CAPRI, several others were hetero-oligomers, or featured multiple interfaces between the same protein pair. For most targets, predictions started from the experimentally determined structures of the free (unbound) components, or from models built from known structures of related or similar proteins. To succeed they therefore needed to account for conformational changes and model inaccuracies. In total, 64 groups and 12 web-servers submitted docking predictions of which 4420 were evaluated. Overall our assessment reveals that 67% of the groups, more than ever before, produced acceptable models or better for at least one target, with many groups submitting multiple high- and medium-accuracy models for two to six targets. Forty-one groups including four web-servers participated in the scoring experiment with 1296 evaluated models. Scoring predictions also show signs of progress evidenced from the large proportion of correct models submitted. But singling out the best models remains a challenge, which also adversely affects the ability to correctly rank docking models. With the increased interest in translating abstract protein interaction networks into realistic models of protein assemblies, the growing CAPRI community is actively developing more efficient and reliable docking and scoring methods for everyone to use. © 2010 Wiley-Liss, Inc.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe
A politics of conversion: nihilism and love in Toni Morrison's fiction
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-Graduação em Letras.O estudo Uma Política de Conversão: Niilismo e Amor na Ficção de Toni Morrison começa com a idéia de que a Literatura Afro-Americana apresenta um sentido de auto-reflexividade e hibridismo, através do qual autobiografia dialoga com romance, o espiritual se funde com o político. A partir deste traço dialógico a auto-reflexividade é politicamente estabelecida entre niilismo e amor. Na política de conversão, o estudo analisa as formas como mulheres negras, individualmente ou em grupo, fogem da escravidão para a liberdade, avançam da individualidade para a coletividade, ou substituem niilismo por amor. Metodologicamente o estudo apresenta sete capítulos. O primeiro discute os aspectos dialógicos que ilustram as conexões entre narrativas espirituais, de escravos e ficção, entre espiritualidade e política. O segundo examina o diálogo entre a conversão, pregação pública e formação da comunidade em Diário e Experiências Religiosas de Lee. O capítulo sugere que ao afirmar espiritualidade e humanidade a narradora abre profundo espaço para a mulher negra reclamar direitos civis. O terceiro discute o diálogo no interior da política de conversão entre narrativa de escravos e ficção. Este diálogo lida com niilismo e amor em Incidentes de Jacobs e Amada, Sula e O Olho Mais Azul de Morrison. Para a análise de niilismo e amor valores individuais e coletivos são considerados em relação a cinco aspectos: ambiente e agente antagonistas, agente de apoio, propósito da personagem e resultado alcançado. É visível, no estudo, o apoio que certas mulheres recebem de suas comunidades para contra-atacar antagonistas. O apoio nem sempre resulta na superação do niilismo e, por isso, derrota temporária pode ocorrer antes que elas sejam reintegradas à comunidade, como acontece com Linda Brent. O quarto capítulo examina as fraquezas e as energias da política da conversão e a reintegração de Sethe Suggs à comunidade de Bluestone Road. O quinto avalia como a comunidade de Bottom tenta controlar a individualidade de Sula Peace e como um grupo de mulheres lideradas por Nel Wrights consegue resgatar o espírito de independência da heroína. O sexto mostra como a política da conversão das mulheres de Lorain é incapaz de garantir a saúde mental de Pecola Breedlove, mas consegue criar um papel mais consistente para o grupo. No sétimo, a conclusão examina da relação dialética entre niilismo e amor ou auto-amor nas experiências dos indivíduos e dos grupos. O estudo sugere que em Incidentes a busca de Linda Brent por liberdade envolve elementos de autodestruição e de autoempoderamento. Da mesma maneira, o estudo conclui que em Amada o amor que Sethe Suggs tem para as suas crianças mata a própria filha, enfatizando, assim, o desejo de livrá-la da escravidão. Igualmente em Sula, a individualidade de Sula Peace não apenas limita, mas também expande as experiências do grupo, levando-o à emancipação. Finalmente, em O Olho Mais Azul a luta de Pecola Breedlove por amor e beleza reflete auto-ódio ao mesmo tempo em que reconstrói a auto-apreciação de toda a comunidade
ASO Author Reflections : Distal Pancreatectomy With and Without Portomesenteric Venous Resection for Pancreatic Adenocarcinoma: A Transatlantic Evaluation of Patients in North America, Germany, Sweden, and The Netherlands (GAPASURG)
No full textn/aThomas F. Stoop is granted by (1) Dutch Cancer Society (KWF) and (2) Deltaplan Alvleesklierkanker for the Dutch PREOPANC-4 trial on multidisciplinary management of LAPC (NCT05524090). Thomas F. Stoop is granted by (3) the Cultuur-fonds (Jan de Ruijsscher / Pia Huisman Fonds) and (4) Cancer Center Amsterdam.</p
Blind predictions of protein interfaces by docking calculations in CAPRI
No full textReliable prediction of the amino acid residues involved in protein-protein interfaces can provide valuable insight into protein function, and inform mutagenesis studies, and drug design applications. A fast-growing number of methods are being proposed for predicting protein interfaces, using structural information, energetic criteria, or sequence conservation or by integrating multiple criteria and approaches. Overall however, their performance remains limited, especially when applied to nonobligate protein complexes, where the individual components are also stable on their own. Here, we evaluate interface predictions derived from protein-protein docking calculations. To this end we measure the overlap between the interfaces in models of protein complexes submitted by 76 participants in CAPRI (Critical Assessment of Predicted Interactions) and those of 46 observed interfaces in 20 CAPRI targets corresponding to nonobligate complexes. Our evaluation considers multiple models for each target interface, submitted by different participants, using a variety of docking methods. Although this results in a substantial variability in the prediction performance across participants and targets, clear trends emerge. Docking methods that perform best in our evaluation predict interfaces with average recall and precision levels of about 60%, for a small majority (60%) of the analyzed interfaces. These levels are significantly higher than those obtained for nonobligate complexes by most extant interface prediction methods. We find furthermore that a sizable fraction (24%) of the interfaces in models ranked as incorrect in the CAPRI assessment are actually correctly predicted (recall and precision ≥50%), and that these models contribute to 70% of the correct docking-based interface predictions overall. Our analysis proves that docking methods are much more successful in identifying interfaces than in predicting complexes, and suggests that these methods have an excellent potential of addressing the interface prediction challenge. © 2010 Wiley-Liss, Inc.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe
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