1,720,959 research outputs found
Molecular simulations to investigate the impact of post-transcriptional modifications on RNA structural dynamics
Full text linkMolecular dynamics simulations of chemically modified ribonucleotides
Full text linkPost-transcriptional modifications are crucial for RNA function, with roles
ranging from the stabilization of functional RNA structures to modulation of
RNA--protein interactions. Additionally, artificially modified RNAs have been
suggested as optimal oligonucleotides for therapeutic purposes. The impact of
chemical modifications on secondary structure has been rationalized for some of
the most common modifications. However, the characterization of how the
modifications affect the three-dimensional RNA structure and dynamics and its
capability to bind proteins is still highly challenging. Molecular dynamics
simulations, coupled with enhanced sampling methods and integration of
experimental data, provide a direct access to RNA structural dynamics. In the
context of RNA chemical modifications, alchemical simulations where a wild type
nucleotide is converted to a modified one are particularly common. In this
Chapter, we review recent molecular dynamics studies of modified
ribonucleotides. We discuss the technical aspects of the reviewed works,
including the employed force fields, enhanced sampling methods, and alchemical
methods, in a way that is accessible to experimentalists. Finally, we provide
our perspective on this quickly growing field of research. The goal of this
Chapter is to provide a guide for experimentalists to understand molecular
dynamics works and, at the same time, give to molecular dynamics experts a
solid review of published articles that will be a useful starting point for new
research.Comment: Submitted as a chapter for the book "RNA Structure and Function",
series "RNA Technologies", published by Springe
Adding alchemical variables to metadynamics to enhance sampling in free energy calculations
Full text linkPerforming alchemical transformations, in which one molecular system is
nonphysically changed to another system, is a popular approach adopted in
performing free energy calculations associated with various biophysical
processes, such as protein-ligand binding or the transfer of a molecule between
environments. While the sampling of alchemical intermediate states in either
parallel (e.g. Hamiltonian replica exchange) or serial manner (e.g. expanded
ensemble) can bridge the high-probability regions in the configurational space
between two end states of interest, alchemical methods can fail in scenarios
where the most important slow degrees of freedom in the configurational space
are in large part orthogonal to the alchemical variable, or if the system gets
trapped in a deep basin extending in both the configurational and alchemical
space.
To alleviate these issues, we propose to use alchemical variables as an
additional dimension in metadynamics, augmenting the ability both to sample
collective variables and to enhance sampling in free energy calculations. In
this study, we validate our implementation of alchemical metadynamics in PLUMED
with test systems and alchemical processes with varying complexities and
dimensions of collective variable space, including the interconversion between
the torsional metastable states of a toy system and the methylation of a
nucleoside both in the isolated form and in a duplex. We show that
multi-dimensional alchemical metadynamics can address the challenges mentioned
above and further accelerate sampling by introducing configurational collective
variables. The method can trivially be combined with other metadynamics-based
algorithms implemented in PLUMED. The necessary PLUMED code changes have
already been released for general use in PLUMED 2.8
Molecular simulations to investigate the impact of N6-methylation in RNA recognition: Improving accuracy and precision of binding free energy prediction
No full text<p>Dataset relative to Molecular dynamics simulation performed for the work "Molecular simulations to investigate the impact of N6-methylation in RNA recognition: Improving accuracy and precision of binding free energy prediction".<br><br>The dataset contains data of 42 alchemical simulations and is subdivided in 4 zip files.<br><br>Folders are named following the scheme: system_configuration_forcefield.<br>Zip file C1 contains .mdp files used for all the simulations.<br><br>Folders corresponding to simulations performed with the fit5_AC ff contains:<br>- topology files (topol.top, topol_RNA_chain_A.itp, topol_RNA_chain_B.itp)<br>- index files needed to reconstruct the demuxed trajectories (replica_index.xvg , replica_index.xvg)<br>- 16 folders, one for each replica (lam0 ... lam15), containing:<br> - final configuration (confout.gro)<br> - log file (md.log)</p>
<p> - input file for md run (md.tpr)<br> - energies for the concatenated trajectories recomputed for the realtive replica hamiltonian (ener_trj_conc.edr)<br><br>Folders corresponding to simlations performed with fit_A parametrization only contains .edr files corresponding to energies for the concatenated trajectory computed for 14 set of DeQs drawn from a gaussian distribution, with the relative topologies.<br><br>Supplementary materials relative to simlations performed with fit_A parametrizationcan be found in: https://zenodo.org/records/6498021</p>
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
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