1,720,959 research outputs found
Steered Molecular Dynamics Simulations Predict Conformational Stability of Glutamate Receptors
Get PDFThe stability of
protein–protein interfaces can be essential
for protein function. For ionotropic glutamate receptors, a family
of ligand-gated ion channels vital for normal function of the central
nervous system, such an interface exists between the extracellular
ligand binding domains (LBDs). In the full-length protein, the LBDs
are arranged as a dimer of dimers. Agonist binding to the LBDs opens
the ion channel, and briefly after activation the receptor desensitizes.
Several residues at the LBD dimer interface are known to modulate
desensitization, and conformational changes around these residues
are believed to be involved in the state transition. The general hypothesis
is that the interface is disrupted upon desensitization, and structural
evidence suggests that the disruption might be substantial. However,
when cross-linking the central part of this interface, functional
data suggest that the receptor can still undergo desensitization,
contradicting the hypothesis of major interface disruption. Here,
we illustrate how opening the dimer interface using steered molecular
dynamics (SMD) simulations, and analyzing the work values required,
provides a quantitative measure for interface stability. For one subtype
of glutamate receptors, which is regulated by ion binding to the dimer
interface, we show that opening the interface without ions bound requires
less work than with ions present, suggesting that ion binding indeed
stabilizes the interface. Likewise, for interface mutants with longer-lived
active states, the interface is more stable, while the work required
to open the interface is reduced for less active mutants. Moreover,
a cross-linked mutant can still undergo initial interface opening
motions similar to the native receptor and at similar energetic cost.
Thus, our results support that interface opening is involved in desensitization.
Furthermore, they provide reconciliation of apparently opposing data
and demonstrate that SMD simulations can give relevant biological
insight into longer time scale processes without the need for expensive
calculations
Protonation States of Important Acidic Residues in the Central Ca<sup>2+</sup> Ion Binding Sites of the Ca<sup>2+</sup>-ATPase: A Molecular Modeling Study
No full textThe P-type ATPases are responsible for the transport
of cations
across cell membranes. The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) transports two Ca2+ ions from the cytoplasm
to the lumen of the sarco(endo)plasmic reticulum and countertransports
two or three protons per catalytic cycle. Two binding sites for Ca2+ ions have been located via protein crystallography, including
four acidic amino acid residues that are essential to the ion coordination.
In this study, we present molecular dynamics (MD) simulations examining
the protonation states of these amino acid residues in a Ca2+-free conformation of SERCA. Such knowledge will be important for
an improved understanding of atomistic details of the transport mechanism
of protons and Ca2+ ions. Eight combinations of the protonation
of four central acidic residues, Glu309, Glu771, Asp800, and Glu908,
are tested from 10 ns MD simulations with respect to protein stability
and ability to maintain a structure similar to the crystal structure.
The trajectories for the most prospective combinations of protonation
states were elongated to 50 ns and subjected to more detailed analysis,
including prediction of pKa values of
the four acidic residues over the trajectories. From the simulations
we find that the combination leaving only Asp800 as charged is most
likely. The results are compared to available experimental data and
explain the observed destabilization upon full deprotonation, resulting
in the entry of cytoplasmic K+ ions into the Ca2+ binding sites during the simulation in which Ca2+ ions
are absent. Furthermore, a hypothesis for the exchange of protons
from the central binding cavity is proposed
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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