Expanded Functionality and Portability for the Colvars Library.

Colvars is an open-source C++ library that provides a modular toolkit for collective-variable-based molecular simulations. It allows practitioners to easily create and implement descriptors that best fit a process of interest and to apply a wide range of biasing algorithms in collective variable space. This paper reviews several features and improvements to Colvars that were added since its original introduction.

Proton Transport Scenarios in Sulfuric Acid Explored via Ab Initio Molecular Dynamics Simulations.

Sulfuric acid (HSO), a highly reactive reagent containing intrinsic protonic charge carriers, has been studied via molecular dynamics simulations. Specifically, we explore the solvation shell structure of the protonic defects, HSO and HSO, as well as the underlying proton transport mechanisms in both the neat and hydrated HSO solutions. Our findings reveal a significant contraction of the dynamic hydrogen-bonded network around the protonic defects, which resembles features seen in water.

Syncopation as structure bootstrapping: the role of asymmetry in rhythm and language.

Syncopation - the occurrence of a musical event on a metrically weak position preceding a rest on a metrically strong position - represents an important challenge in the study of the mapping between rhythm and meter. In this contribution, we present the hypothesis that syncopation is an effective strategy to elicit the bootstrapping of a multi-layered, hierarchically organized metric structure from a linear rhythmic surface. The hypothesis is inspired by a parallel with the problem of linearization in natural language syntax, which is the problem of how hierarchically organized phrase-structure markers are mapped onto linear sequences of words.

Implications of the three-dimensional chromatin organization for genome evolution in a fungal plant pathogen.

The spatial organization of eukaryotic genomes is linked to their biological functions, although it is not clear how this impacts the overall evolution of a genome. Here, we uncover the three-dimensional (3D) genome organization of the phytopathogen Verticillium dahliae, known to possess distinct genomic regions, designated adaptive genomic regions (AGRs), enriched in transposable elements and genes that mediate host infection. Short-range DNA interactions form clear topologically associating domains (TADs) with gene-rich boundaries that show reduced levels of gene expression and reduced genomic variation.

Membrane free-energy landscapes derived from atomistic dynamics explain nonuniversal cholesterol-induced stiffening.

All lipid membranes have inherent morphological preferences and resist deformation. Yet adaptations in membrane shape can and do occur at multiple length scales. While this plasticity is crucial for cellular physiology, the factors controlling the morphological energetics of lipid bilayers and the dominant mechanisms of membrane remodeling remain to be fully understood.

Membrane free-energy landscapes derived from atomistic dynamics explain nonuniversal cholesterol-induced stiffening.

Unlabelled: All lipid membranes have inherent morphological preferences and resist deformation. Yet adaptations in membrane shape can and do occur at multiple length scales. While this plasticity is crucial for cellular physiology, the factors controlling the morphological energetics of lipid bilayers and the dominant mechanisms of membrane remodeling remain unclear.

Fungal dual-domain LysM effectors undergo chitin-induced intermolecular, and not intramolecular, dimerization.

Chitin is a homopolymer of β-(1,4)-linked N-acetyl-D-glucosamine (GlcNAc) and a major structural component of fungal cell walls. In plants, chitin acts as a microbe-associated molecular pattern (MAMP) that is recognized by lysin motif (LysM)-containing plant cell surface-localized pattern recognition receptors (PRRs) that activate a plethora of downstream immune responses. To deregulate chitin-induced plant immunity and successfully establish infection, many fungal pathogens secrete LysM domain-containing effector proteins during host colonization.

SPICA Force Field for Proteins and Peptides.

A coarse-grained (CG) model for peptides and proteins was developed as an extension of the Surface Property fItting Coarse grAined (SPICA) force field (FF). The model was designed to examine membrane proteins that are fully compatible with the lipid membranes of the SPICA FF. A preliminary version of this protein model was created using thermodynamic properties, including the surface tension and density in the SPICA (formerly called SDK) FF.

Human Learning for Molecular Simulations: The Collective Variables Dashboard in VMD.

The Collective Variables Dashboard is a software tool for real-time, seamless exploration of molecular structures and trajectories in a customizable space of collective variables. The Dashboard arises from the integration of the Collective Variables Module (also known as Colvars) with the visualization software VMD, augmented with a fully discoverable graphical interface offering interactive workflows for the design and analysis of collective variables. Typical use cases include a priori design of collective variables for enhanced sampling and free energy simulations as well as analysis of any type of simulation or collection of structures in a collective variable space.

Bringing discrete-time Langevin splitting methods into agreement with thermodynamics.

In light of the recently published complete set of statistically correct Grønbech-Jensen (GJ) methods for discrete-time thermodynamics, we revise a differential operator splitting method for the Langevin equation in order to comply with the basic GJ thermodynamic sampling features, namely, the Boltzmann distribution and Einstein diffusion, in linear systems. This revision, which is based on the introduction of time scaling along with flexibility of a discrete-time velocity attenuation parameter, provides a direct link between the ABO splitting formalism and the GJ methods. This link brings about the conclusion that any GJ method has at least weak second order accuracy in the applied time step.

The Interspecific Fungal Hybrid Displays Subgenome-Specific Gene Expression.

Hybridization is an important evolutionary mechanism that can enable organisms to adapt to environmental challenges. It has previously been shown that the fungal allodiploid species Verticillium longisporum, the causal agent of verticillium stem striping in rapeseed, originated from at least three independent hybridization events between two haploid species. To reveal the impact of genome duplication as a consequence of hybridization, we studied the genome and transcriptome dynamics upon two independent V.

Adaptive evolution of Moniliophthora PR-1 proteins towards its pathogenic lifestyle.

Background: Plant pathogenesis related-1 (PR-1) proteins belong to the CAP superfamily and have been characterized as markers of induced defense against pathogens. Moniliophthora perniciosa and Moniliophthora roreri are hemibiotrophic fungi that respectively cause the witches' broom disease and frosty pod rot in Theobroma cacao. Interestingly, a large number of plant PR-1-like genes are present in the genomes of both species and many are up-regulated during the biotrophic interaction.

MAMP-triggered Medium Alkalinization of Plant Cell Cultures.

Plants recognize a wide variety of microbial molecules to detect and respond to potential invaders. Recognition of Microbe-Associated Molecular Patterns (MAMPs) by cell surface receptors initiate a cascade of biochemical responses that include, among others, ion fluxes across the plasma membrane. A consequence of such event is a decrease in the concentration of extracellular H ions, which can be experimentally detected in plant cell suspensions as a shift in the pH of the medium.

Data-guided Multi-Map variables for ensemble refinement of molecular movies.

Driving molecular dynamics simulations with data-guided collective variables offer a promising strategy to recover thermodynamic information from structure-centric experiments. Here, the three-dimensional electron density of a protein, as it would be determined by cryo-EM or x-ray crystallography, is used to achieve simultaneously free-energy costs of conformational transitions and refined atomic structures. Unlike previous density-driven molecular dynamics methodologies that determine only the best map-model fits, our work employs the recently developed Multi-Map methodology to monitor concerted movements within equilibrium, non-equilibrium, and enhanced sampling simulations.

The challenge of stochastic Størmer-Verlet thermostats generating correct statistics.

In light of the recently developed complete GJ set of single random variable stochastic, discrete-time Størmer-Verlet algorithms for statistically accurate simulations of Langevin equations [N. Grønbech-Jensen, Mol. Phys.

Repetitive Elements Contribute to the Diversity and Evolution of Centromeres in the Fungal Genus .

Centromeres are chromosomal regions that are crucial for chromosome segregation during mitosis and meiosis, and failed centromere formation can contribute to chromosomal anomalies. Despite this conserved function, centromeres differ significantly between and even within species. Thus far, systematic studies into the organization and evolution of fungal centromeres remain scarce.

Scalable molecular dynamics on CPU and GPU architectures with NAMD.

NAMDis a molecular dynamics program designed for high-performance simulations of very large biological objects on CPU- and GPU-based architectures. NAMD offers scalable performance on petascale parallel supercomputers consisting of hundreds of thousands of cores, as well as on inexpensive commodity clusters commonly found in academic environments. It is written in C++ and leans on Charm++ parallel objects for optimal performance on low-latency architectures.

Coexistence of Lipid Phases Stabilizes Interstitial Water in the Outer Layer of Mammalian Skin.

The lipid matrix in the outer layer of mammalian skin, the stratum corneum, has been previously investigated by multiple biophysical techniques aimed at identifying hydrophilic and lipophilic pathways of permeation. Although consensus is developing over the microscopic structure of the lipid matrix, no molecular-resolution model describes the permeability of all chemical species simultaneously. Using molecular dynamics simulations of a model mixture of skin lipids, the self-assembly of the lipid matrix lamellae has been studied.

Large-scale state-dependent membrane remodeling by a transporter protein.

That channels and transporters can influence the membrane morphology is increasingly recognized. Less appreciated is that the extent and free-energy cost of these deformations likely varies among different functional states of a protein, and thus, that they might contribute significantly to defining its mechanism. We consider the trimeric Na-aspartate symporter Glt, a homolog of an important class of neurotransmitter transporters, whose mechanism entails one of the most drastic structural changes known.

Direct Derivation of Free Energies of Membrane Deformation and Other Solvent Density Variations From Enhanced Sampling Molecular Dynamics.

We report a methodology to calculate the free energy of a shape transformation in a lipid membrane directly from a molecular dynamics simulation. The bilayer need not be homogeneous or symmetric and can be atomically detailed or coarse grained. The method is based on a collective variable that quantifies the similarity between the membrane and a set of predefined density distributions.

Structural Characterization of Biomolecules through Atomistic Simulations Guided by DEER Measurements.

Double electron-electron resonance (DEER) is a popular technique that exploits attached spin labels to probe the collective dynamics of biomolecules in a native environment. Like most spectroscopic approaches, DEER detects an ensemble of states accounting for biomolecular dynamics as well as the labels' intrinsic flexibility. Hence, the DEER data alone do not provide high-resolution structural information.

Suppression of Plant Immunity by Fungal Chitinase-like Effectors.

Crop diseases caused by fungi constitute one of the most important problems in agriculture, posing a serious threat to food security [1]. To establish infection, phytopathogens interfere with plant immune responses [2, 3]. However, strategies to promote virulence employed by fungal pathogens, especially non-model organisms, remain elusive [4], mainly because fungi are more complex and difficult to study when compared to the better-characterized bacterial pathogens.

No evidence for cerebellar abnormality in adults with developmental dyslexia.

Developmental dyslexia is commonly believed to result from a deficiency in the recognition and processing of speech sounds. According to the cerebellar deficit hypothesis, this phonological deficit is caused by deficient cerebellar function. In the current study, 26 adults with developmental dyslexia and 25 non-dyslexic participants underwent testing of reading-related skills, cerebellar functions, and MRI scanning of the brain.

Mechanically Strong Polymer Sheets from Aligned Ultrahigh-Molecular-Weight Polyethylene Nanocomposites.

Ultrahigh-molecular-weight polyethylene (UHMWPE) is of great interest as a next-generation body armor material because of its superior mechanical properties. However, such unique properties depend critically on its microscopic structure characteristics, including the degree of crystallinity, chain alignment, and morphology. Here, we present a highly aligned UHMWPE and its composite sheets containing uniformly dispersed boron nitride (BN) nanosheets.