CABS-flex predictions of protein flexibility compared with NMR ensembles

Motivation: Identification of flexible regions of protein structures is important for understanding of their biological functions. Recently, we have developed a fast approach for predicting protein structure fluctuations from a single protein model: the CABS-flex. CABS-flex was shown to be an efficient alternative to conventional all-atom molecular dynamics (MD). In this work, we evaluate CABS-flex and MD predictions by comparison with protein structural variations within NMR ensembles. Results: Based on a benchmark set of 140 proteins, we show that the relative fluctuations of protein residues obtained from CABS-flex are well correlated to those of NMR ensembles. On average, this correlation is stronger than that between MD and NMR ensembles. In conclusion, CABS-flex is useful and complementary to MD in predicting of protein regions that undergo conformational changes and the extent of such changes

Combining Coarse-Grained Protein Models with Replica-Exchange All-Atom Molecular Dynamics

We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic details, conformations derived from the CABS simulation were subjected to replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb force fields in explicit solvent. Such a combination accelerates system convergence several times in comparison with all-atom simulations starting from the extended chain conformation, demonstrated by the analysis of melting curves, the number of native-like conformations as a function of time and secondary structure propagation. The results strongly suggest that the proposed multiscale method could be an efficient and accurate tool for high-resolution studies of protein folding dynamics in larger systems.Comment: 12 pages, 4 figure

Semantic Distance Modulates the N400 Event-Related Potential in Verbal Analogical Reasoning

Computational accounts have traditionally focused on mapping between structured representations as fundamental to analogical processing. However, a recent connectionist model has been used to argue that structured representations may not be necessary to solve verbal analogies. Green and colleagues (2010) have shown that brain areas associated with analogical mapping become more engaged as semantic distance increases between verbal analogy source and targets. Herein, we had participants verify verbal analogies characterized for semantic distance while we monitored their brain waves using EEG. Our results suggest that the semantic distance between the source and target of a verbal analogy does influence early semantic processing as reflected in the N400 Event-Related Potential. However, successfully differentiating valid and invalid verbal analogies engages areas of prefrontal cortex widely associated with inhibitory processing and the integration of abstract relations in working memory. Thus, it appears that traditional semantic priming alone is likely insufficient to explain the full extent of analogical processing

CABS-flex 2.0: a web server for fast simulations of flexibility of protein structures

Classical simulations of protein flexibility remain computationally expensive, especially for large proteins. A few years ago, we developed a fast method for predicting protein structure fluctuations that uses a single protein model as the input. The method has been made available as the CABS-flex web server and applied in numerous studies of protein structure-function relationships. Here, we present a major update of the CABS-flex web server to version 2.0. The new features include: extension of the method to significantly larger and multimeric proteins, customizable distance restraints and simulation parameters, contact maps and a new, enhanced web server interface. CABS-flex 2.0 is freely available at http://biocomp.chem.uw.edu.pl/CABSflex

Highly flexible protein-peptide docking using CABS-dock

Protein-peptide molecular docking is a difficult modeling problem. It is even more challenging when significant conformational changes that may occur during the binding process need to be predicted. In this chapter, we demonstrate the capabilities and features of the CABS-dock server for flexible protein-peptide docking. CABS-dock allows highly efficient modeling of full peptide flexibility and significant flexibility of a protein receptor. During CABS-dock docking, the peptide folding and binding process is explicitly simulated and no information about the peptide binding site or its structure, is used. This chapter presents a successful CABS-dock use for docking a potentially therapeutic peptide to a protein target. Moreover, simulation contact maps, a new CABS-dock feature, are described and applied to the docking test case. Finally, a tutorial for running CABS-dock from the command line or command line scripts is provided. The CABS-dock web server is available from http://biocomp.chem.uw.edu.pl/CABSdock

Aprendizagem Histórica e narrativas históricas de jovens estudantes sobre a Guerra do Paraguai: uma experiência PDE

Anais do XVII Congresso Internacional das Jornadas de Educaão História - teoria, pesquisa e prática - I Encontro da AIPEDH - Associação Iber-Americana de Pesquisadores em Educação História, realizado pela Universidade Federal da Integração Latino-Americana, entre 02, 03 e 04 de agosto de 2017.Este texto tem por objetivo apresentar as reflexões teóricas que fundamentam a implementação didático-pedagógica em fase de execução, de um trabalho de pesquisa do Programa de Desenvolvimento Educacional (PDE). Buscando desenvolver uma nova relação dos jovens estudantes com a História e favorecer a aprendizagem histórica, este estudo encontrou fundamentos no aporte teórico da Educação Histórica e da consciência histórica. Para Rüsen (2014) a consciência histórica é a combinação entre a apreensão do passado pela necessidade de entender o presente e de presumir o futuro, expressa por meio das narrativas históricas, isto é, da constituição de sentido, expresso por meio da linguagem. O conteúdo substantivo é a Guerra do Paraguai e a metodologia de pesquisa contempla a produção de narrativas históricas a partir do estudo de fontes históricas acerca da temáticaUFP