Mechanical causes and implications of repetitive DNA motifs.

Experimental research suggests that local patterns in DNA sequences can result in stiffer or more curved structures, potentially impacting chromatin formation, transcription regulation, and other processes. However, the effect of sequence variation on DNA geometry and mechanics remains relatively underexplored. Using rigid base pair models to aid rapid computation, we investigated the sample space of 100 bp DNA sequences to identify mechanical extrema based on metrics such as static persistence length, global bend, or angular deviation.

Reversions mask the contribution of adaptive evolution in microbiomes.

When examining bacterial genomes for evidence of past selection, the results depend heavily on the mutational distance between chosen genomes. Even within a bacterial species, genomes separated by larger mutational distances exhibit stronger evidence of purifying selection as assessed by d/d, the normalized ratio of nonsynonymous to synonymous mutations. Here, we show that the classical interpretation of this scale dependence, weak purifying selection, leads to problematic mutation accumulation when applied to available gut microbiome data.

Reversions mask the contribution of adaptive evolution in microbiomes.

When examining bacterial genomes for evidence of past selection, the results obtained depend heavily on the mutational distance between chosen genomes. Even within a bacterial species, genomes separated by larger mutational distances exhibit stronger evidence of purifying selection as assessed by , the normalized ratio of nonsynonymous to synonymous mutations. Here, we show that the classical interpretation of this scale-dependence, weak purifying selection, leads to problematic mutation accumulation when applied to available gut microbiome data.

A Suite of Tutorials for the WESTPA 2.0 Rare-Events Sampling Software [Article v2.0].

The weighted ensemble (WE) strategy has been demonstrated to be highly efficient in generating pathways and rate constants for rare events such as protein folding and protein binding using atomistic molecular dynamics simulations. Here we present two sets of tutorials instructing users in the best practices for preparing, carrying out, and analyzing WE simulations for various applications using the WESTPA software. The first set of more basic tutorials describes a range of simulation types, from a molecular association process in explicit solvent to more complex processes such as host-guest association, peptide conformational sampling, and protein folding.

WESTPA 2.0: High-Performance Upgrades for Weighted Ensemble Simulations and Analysis of Longer-Timescale Applications.

The weighted ensemble (WE) family of methods is one of several statistical mechanics-based path sampling strategies that can provide estimates of key observables (rate constants and pathways) using a fraction of the time required by direct simulation methods such as molecular dynamics or discrete-state stochastic algorithms. WE methods oversee numerous parallel trajectories using intermittent overhead operations at fixed time intervals, enabling facile interoperability with any dynamics engine. Here, we report on the major upgrades to the WESTPA software package, an open-source, high-performance framework that implements both basic and recently developed WE methods.

A Minimal, Adaptive Binning Scheme for Weighted Ensemble Simulations.

A promising approach for simulating rare events with rigorous kinetics is the weighted ensemble path sampling strategy. One challenge of this strategy is the division of configurational space into bins for sampling. Here we present a minimal adaptive binning (MAB) scheme for the automated, adaptive placement of bins along a progress coordinate within the framework of the weighted ensemble strategy.

A Suite of Tutorials for the WESTPA Rare-Events Sampling Software [Article v1.0].

The weighted ensemble (WE) strategy has been demonstrated to be highly efficient in generating pathways and rate constants for rare events such as protein folding and protein binding using atomistic molecular dynamics simulations. Here we present five tutorials instructing users in the best practices for preparing, carrying out, and analyzing WE simulations for various applications using the WESTPA software. Users are expected to already have significant experience with running standard molecular dynamics simulations using the underlying dynamics engine of interest (e.