Extended Quality (eQual): Radial threshold clustering based on n-ary similarity.

We are transforming Radial Threshold Clustering (RTC), an algorithm, into Extended Quality Clustering, an algorithm with several novel features. Daura et al's RTC algorithm is a partitioning clustering algorithm that groups similar frames together based on their similarity to the seed configuration. Two current issues with RTC is that it scales as making it inefficient at high frame counts, and the clustering results are dependent on the order of the input frames.

modXNA: A Modular Approach to Parametrization of Modified Nucleic Acids for Use with Amber Force Fields.

Modified nucleic acids have surged as a popular therapeutic route, emphasizing the importance of nucleic acid research in drug discovery and development. Beyond well-known RNA vaccines, antisense oligonucleotides and aptamers can incorporate various modified nucleic acids to target specific biomolecules for various therapeutic activities. Molecular dynamics simulations can accelerate the design and development of these systems with noncanonical nucleic acids by observing intricate dynamic properties and relative stability on the all-atom level.

CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.

Since its inception nearly a half century ago, CHARMM has been playing a central role in computational biochemistry and biophysics. Commensurate with the developments in experimental research and advances in computer hardware, the range of methods and applicability of CHARMM have also grown. This review summarizes major developments that occurred after 2009 when the last review of CHARMM was published.

k-Means NANI: An Improved Clustering Algorithm for Molecular Dynamics Simulations.

One of the key challenges of -means clustering is the seed selection or the initial centroid estimation since the clustering result depends heavily on this choice. Alternatives such as -means++ have mitigated this limitation by estimating the centroids using an empirical probability distribution. However, with high-dimensional and complex data sets such as those obtained from molecular simulation, -means++ fails to partition the data in an optimal manner.

k-Means NANI: an improved clustering algorithm for Molecular Dynamics simulations.

One of the key challenges of -means clustering is the seed selection or the initial centroid estimation since the clustering result depends heavily on this choice. Alternatives such as -means++ have mitigated this limitation by estimating the centroids using an empirical probability distribution. However, with high-dimensional and complex datasets such as those obtained from molecular simulation, -means++ fails to partition the data in an optimal manner.

'A kindergarten teacher must have 100 eyes and 100 ears!': Kindergarten teachers' experiences coping with child sexual abuse and problematic sexual behavior.

Background: Child sexual abuse (CSA) and problematic sexual behavior (PSB) are worldwide phenomena that occur across all ages. Kindergarten teachers' proactive involvement can be crucial to the prevention, disclosure and intervention of CSA and PSB. However, research on their experiences of contending with CSA and PSB remains limited.

International consensus statement on the design, delivery and evaluation of sport-based interventions aimed at promoting social, psychological and physical well-being in prison.

Objective: To develop an international consensus statement to advise on designing, delivering and evaluating sport-based interventions (SBIs) aimed at promoting social, psychological and physical well-being in prison.

Design: Modified Delphi using two rounds of survey questionnaires and two consensus workshops.

Participants: A multidisciplinary panel of more than 40 experts from 15 international jurisdictions was formed, including representation from the following groups and stakeholders: professionals working in the justice system; officials from sport federations and organisations; academics with research experience of prisons, secure forensic mental health settings and SBIs; and policy-makers in criminal justice and sport.

MPI-parallelization of the grid inhomogeneous solvation theory calculation.

The grid inhomogeneous solvation theory (GIST) method requires the often time-consuming calculation of water-water and water-solute energy on a grid. Previous efforts to speed up this calculation include using OpenMP, GPUs, and particle mesh Ewald. This article details how the speed of this calculation can be increased by parallelizing it with MPI, where trajectory frames are divided among multiple processors.

AmberTools.

AmberTools is a free and open-source collection of programs used to set up, run, and analyze molecular simulations. The newer features contained within AmberTools23 are briefly described in this Application note.

Methodological reflections on artistically illustrating ethnographic text from a study of sport pedagogy in youth detention: Ethics, affect, and description.

While there is a burgeoning body of literature on visual methods in ethnography, including drawing and illustration as method for collecting and exploring data, little has been written about how artistic illustrations can be used as a representational method for finished ethnographic texts. Based on an illustrated ethnography-a PhD thesis on sport pedagogy in youth detention-this paper explores what artistic illustrations can do for representations of ethnographic texts. An important starting point of the paper is that artistic illustrations are purpose-full-they can be used strategically to highlight some details over others, thus making it possible for researchers to selectively accomplish several aims when it comes to representation.

Quantifying the effects of lossy compression on energies calculated from molecular dynamics trajectories.

Molecular dynamics (MD) simulations are now able to routinely reach timescales of microseconds and beyond. This has led to a corresponding increase in the amount of MD trajectory data that needs to be stored, particularly when those trajectories contain explicit solvent molecules. As such, it is desirable to be able to compress trajectory data while still retaining as much of the original information as possible.

School principals coping with child sexual abuse in their schools.

Background: Schools serve a central role in prevention, disclosure and intervention in cases of child sexual abuse (CSA). As school principals often face CSA cases in their daily work, they may hold the key to making social change on this front. However, research on principals' experiences of contending with CSA remains limited.

prepareforleap: An automated tool for fast PDB-to-parameter generation.

Setting up molecular dynamics simulations from experimentally determined structures is often complicated by a variety of factors, particularly the inclusion of carbohydrates, since these have several anomer types which can be linked in a variety of ways. Here we present a stand-alone tool implemented in the widely-used software CPPTRAJ that can be used to automate building structures and generating a "ready to run" parameter and coordinate file pair. This tool automatically identifies carbohydrate anomer type, configuration, linkage, and functional groups, and performs topology modifications (e.

Thermodynamic Decomposition of Solvation Free Energies with Particle Mesh Ewald and Long-Range Lennard-Jones Interactions in Grid Inhomogeneous Solvation Theory.

Grid Inhomogeneous Solvation Theory (GIST) maps out solvation thermodynamic properties on a fine meshed grid and provides a statistical mechanical formalism for thermodynamic end-state calculations. However, differences in how long-range nonbonded interactions are calculated in molecular dynamics engines and in the current implementation of GIST have prevented precise comparisons between free energies estimated using GIST and those from other free energy methods such as thermodynamic integration (TI). Here, we address this by presenting PME-GIST, a formalism by which particle mesh Ewald (PME)-based electrostatic energies and long-range Lennard-Jones (LJ) energies are decomposed and assigned to individual atoms and the corresponding voxels they occupy in a manner consistent with the GIST approach.

Improving the speed of volumetric density map generation via cubic spline interpolation.

Visualizing data generated from molecular dynamics simulations can be difficult, particularly when there can be thousands to millions of trajectory frames. The creation of a 3D grid of atomic density (i.e.

A protocol for preparing explicitly solvated systems for stable molecular dynamics simulations.

Before beginning the production phase of molecular dynamics simulations, i.e., the phase that produces the data to be analyzed, it is often necessary to first perform a series of one or more preparatory minimizations and/or molecular dynamics simulations in order to ensure that subsequent production simulations are stable.

Sleep, Noninvasive Brain Stimulation, and the Aging Brain: Challenges and Opportunities.

As we age, sleep patterns undergo severe modifications of their micro and macrostructure, with an overall lighter and more fragmented sleep structure. In general, interventions targeting sleep represent an excellent opportunity not only to maintain life quality in the healthy aging population, but also to enhance cognitive performance and, when pathology arises, to potentially prevent/slow down conversion from e.g.

Protonation state of the selectivity filter of bacterial voltage-gated sodium channels is modulated by ions.

The selectivity filter (SF) of bacterial voltage-gated sodium channels consists of four glutamate residues arranged in a C symmetry. The protonation state population of this tetrad is unclear. To address this question, we simulate the pore domain of bacterial voltage-gated sodium channel of Magnetococcus sp.

Best Practices for Quantification of Uncertainty and Sampling Quality in Molecular Simulations [Article v1.0].

The quantitative assessment of uncertainty and sampling quality is essential in molecular simulation. Many systems of interest are highly complex, often at the edge of current computational capabilities. Modelers must therefore analyze and communicate statistical uncertainties so that "consumers" of simulated data understand its significance and limitations.

Parallelization of CPPTRAJ enables large scale analysis of molecular dynamics trajectory data.

Advances in biomolecular simulation methods and access to large scale computer resources have led to a massive increase in the amount of data generated. The key enablers have been optimization and parallelization of the simulation codes. However, much of the software used to analyze trajectory data from these simulations is still run in serial, or in some cases many threads via shared memory.

Computational Assessment of Potassium and Magnesium Ion Binding to a Buried Pocket in GTPase-Associating Center RNA.

An experimentally well-studied model of RNA tertiary structures is a 58mer rRNA fragment, known as GTPase-associating center (GAC) RNA, in which a highly negative pocket walled by phosphate oxygen atoms is stabilized by a chelated cation. Although such deep pockets with more than one direct phosphate to ion chelation site normally include magnesium, as shown in one GAC crystal structure, another GAC crystal structure and solution experiments suggest potassium at this site. Both crystal structures also depict two magnesium ions directly bound to the phosphate groups comprising this controversial pocket.

Molecular basis for the broad substrate selectivity of a peptide prenyltransferase.

The cyanobactin prenyltransferases catalyze a series of known or unprecedented reactions on millions of different substrates, with no easily observable recognition motif and exquisite regioselectivity. Here we define the basis of broad substrate tolerance for the otherwise uncharacterized TruF family. We determined the structures of the Tyr-prenylating enzyme PagF, in complex with an isoprenoid donor analog and a panel of linear and macrocyclic peptide substrates.

Using Wavelet Analysis To Assist in Identification of Significant Events in Molecular Dynamics Simulations.

Long time scale molecular dynamics (MD) simulations of biological systems are becoming increasingly commonplace due to the availability of both large-scale computational resources and significant advances in the underlying simulation methodologies. Therefore, it is useful to investigate and develop data mining and analysis techniques to quickly and efficiently extract the biologically relevant information from the incredible amount of generated data. Wavelet analysis (WA) is a technique that can quickly reveal significant motions during an MD simulation.

Highly sampled tetranucleotide and tetraloop motifs enable evaluation of common RNA force fields.

Recent modifications and improvements to standard nucleic acid force fields have attempted to fix problems and issues that have been observed as longer timescale simulations have become routine. Although previous work has shown the ability to fold the UUCG stem-loop structure, until now no group has attempted to quantify the performance of current force fields using highly converged structural populations of the tetraloop conformational ensemble. In this study, we report the use of multiple independent sets of multidimensional replica exchange molecular dynamics (M-REMD) simulations with different initial conditions to generate well-converged conformational ensembles for the tetranucleotides r(GACC) and r(CCCC), as well as the larger UUCG tetraloop motif.

On the absence of intrahelical DNA dynamics on the μs to ms timescale.

DNA helices display a rich tapestry of motion on both short (<100 ns) and long (>1 ms) timescales. However, with the exception of mismatched or damaged DNA, experimental measures indicate that motions in the 1 μs to 1 ms range are effectively absent, which is often attributed to difficulties in measuring motions in this time range. We hypothesized that these motions have not been measured because there is effectively no motion on this timescale, as this provides a means to distinguish faithful Watson-Crick base-paired DNA from damaged DNA.