1,720,980 research outputs found
Coarse-grained modelling of protein structure and internal dynamics: comparative methods and applications
Full text linkThe first chapter is devoted to a brief summary of the basic techniques commonly
used to characterise protein's internal dynamics, and to perform those primary analyses
which are the basis for our further developments. To this purpose we recall the
basics of Principal Component Analysis of the covariance matrix of molecular dynamics
(MD) trajectories. The overview is aimed at motivating and justifying a posteriori the
introduction of coarse-grained models of proteins.
In the second chapter we shall discuss dynamical features shared by different conformers
of a protein. We'll review previously obtained results, concerning the universality
of the vibrational spectrum of globular proteins and the self-similar free energy
landscape of specific molecules, namely the G-protein and Adk. Finally, a novel technique
will be discussed, based on the theory of Random Matrices, to extract the robust
collective coordinates in a set of protein conformers by comparison with a stochastic
reference model.
The third chapter reports on an extensive investigation of protein internal dynamics
modelled in terms of the relative displacement of quasi-rigid groups of amino acids.
Making use of the results obtained in the previous chapters, we shall discuss the development
of a strategy to optimally partition a protein in units, or domains, whose
internal strain is negligible compared to their relative
uctuation. These partitions will
be used in turn to characterise the dynamical properties of proteins in the framework
of a simplified, coarse-grained, description of their motion.
In the fourth chapter we shall report on the possibility to use the collective
uctuations
of proteins as a guide to recognise relationships between them that may not be
captured as significant when sequence or structural alignment methods are used. We
shall review a method to perform the superposition of two proteins optimising the similarity
of the structures as well as the dynamical consistency of the aligned regions; then,
we shall next discuss a generalisation of this scheme to accelerate the dynamics-based
alignment, in the perspective of dataset-wide applications.
Finally, the fifth chapter focuses on a different topic, namely the occurrence of
topologically-entangled states (knots) in proteins. Specifically, we shall investigate
the sequence and structural properties of knotted proteins, reporting on an exhaustive
dataset-wide comparison with unknotted ones. The correspondence, or the lack thereof,
between knotted and unknotted proteins allowed us to identify, in knotted chains, small
segments of the backbone whose `virtual' excision results in an unknotted structure.
These `knot-promoting' loops are thus hypothesised to be involved in the formation of
the protein knot, which in turn is likely to cover some role in the biological function of
the knotted proteins
PiSQRD: a web server for decomposing proteins into quasirigid dynamical domains
No full textSummary: The PiSQRD web resource can be used to subdivide protein structures in quasi-rigid dynamical domains. The latter are groups of amino acids behaving as approximately-rigid units in the course of protein equilibrium fluctuations. The PiSQRD server takes as input a biomolecular structure and the desired fraction of protein internal fluctuations that must be accounted for by the relative rigid-body motion of the dynamical domains. Next, the lowest-energy modes of fluctuation of the protein (optionally provided by the user) are calculated and used to identify the rigid subunits. The resulting optimal subdivision is returned through a web page containing both interactive graphics and detailed data output
Corresponding Functional Dynamics across the Hsp90 Chaperone Family: Insights from a Multiscale Analysis of MD Simulations
No full textUnderstanding how local protein modifications, such as binding small-molecule ligands, can trigger and regulate large-scale motions of large protein domains is a major open issue in molecular biology. We address various aspects of this problem by analyzing and comparing atomistic simulations of Hsp90 family representatives for which crystal structures of the full length protein are available: mammalian Grp94, yeast Hsp90 and E.coli HtpG. These chaperones are studied in complex with the natural ligands ATP, ADP and in the Apo state. Common key aspects of their functional dynamics are elucidated with a novel multi-scale comparison of their internal dynamics. Starting from the atomic resolution investigation of internal fluctuations and geometric strain patterns, a novel analysis of domain dynamics is developed. The results reveal that the ligand-dependent structural modulations mostly consist of relative rigid-like movements of a limited number of quasi-rigid domains, shared by the three proteins. Two common primary hinges for such movements are identified. The first hinge, whose functional role has been demonstrated by several experimental approaches, is located at the boundary between the N-terminal and Middle-domains. The second hinge is located at the end of a three-helix bundle in the Middle-domain and unfolds/unpacks going from the ATP- to the ADP-state. This latter site could represent a promising novel druggable allosteric site common to all chaperones
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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