Molecular Timescale Research Articles

Anomalous friction of supercooled glycerol on mica

Although friction of liquids on solid surfaces is traditionally linked to wettability, recent works have unveiled the role of the solid’s internal excitations on interfacial dissipation. In order to directly evidence such couplings, we take advantage of the considerable variation of the molecular timescales of supercooled glycerol under mild change of temperature to explore how friction depends on the liquid’s molecular dynamics. Using a dedicated tuning-fork AFM, we measure the slippage of glycerol on mica. We report a 100 fold increase of slip length upon cooling, while liquid-solid friction exhibits a linear scaling with molecular relaxation rate at high temperature. This scaling can be explained by a contribution of mica’s phonons which resonate with density fluctuations in the liquid, allowing efficient momentum transfer to mica. These results suggest that engineering phononic spectra of materials could enhance flow performance in nanofluidic channels and industrially relevant membranes.

Developmental biology of Spiralicellula and the Ediacaran origin of crown metazoans.

The early Ediacaran Weng'an biota (Doushantuo Formation, South China) provides a rare window onto the period of Earth history in which molecular timescales have inferred the initial phase of crown-metazoan diversification. Interpretation of the embryo-like fossils that dominate the biota remains contentious because they are morphologically simple and so difficult to constrain phylogenetically. Spiralicellula from the Weng'an biota is distinguished by spiral internal bodies, allied through development to Megasphaera or Helicoforamina and interpreted variously as metazoan embryos, encysting protists, or chlorophycean green algae. Here we show, using X-ray microtomography, that Spiralicellula has a single-layered outer envelope and no more than 32 internal cells, often preserving a nucleus and yolk granules. There is no correlation between the extent of spiral development and the number of component cells; rather, the spiral developed with each palintomic stage, associated with cell disaggregation and reorientation. Evidence for envelope thinning and cell loss was observed in all developmental stages, reflecting non-deterministic shedding of gametes or amoebae. The developmental biology of Spiralicellula is similar to Megasphaera and Helicoforamina, which otherwise exhibit more rounds of palintomy. We reject a crown-metazoan affinity for Spiralicellula and all other components of the Weng'an biota, diminishing the probability of crown-metazoan diversification before the early Ediacaran.

Microscopic insights on ion transport in Li3OCl1−xBrx anti-perovskites from metadynamics simulations

The recently discovered anti-perovskites of the formula, Li3OCl1−xBrx, where x=0 to 1, have been garnering interest as potential candidates for solid electrolytes in battery applications. It is observed that the Li ion transport in these solids is rather slow, and unaccessible within typical molecular dynamics time scales. However, by judicially augmenting it with the accelerated sampling technique of metadynamics, the present study derives fresh insights on the nature of Li ion transport in these systems. The microscopic of ion migration along intra- and inter-octahedral channels, suggests that intra-octahedral channels account for over 95% Li transport in the system. The bromide end member offers lower free energy barriers, due to entropic factors resulting from the expansion of the lattice. However, the large free energy barriers estimated in the present work suggest that the undoped Li3OCl1−xBrx anti-perovskites are unlikely to exhibit superionic behavior.

Mapping the recognition pathway of cyclobutane pyrimidine dimer in DNA by Rad4/XPC.

UV radiation-induced DNA damages have adverse effects on genome integrity and cellular function. The most prevalent UV-induced DNA lesion is the cyclobutane pyrimidine dimer (CPD), which can cause skin disorders and cancers in humans. Rad4/XPC is a damage sensing protein that recognizes and repairs CPD lesions with high fidelity. However, the molecular mechanism of how Rad4/XPC interrogates CPD lesions remains elusive. Emerging viewpoints indicate that the association of Rad4/XPC with DNA, the insertion of a lesion-sensing β-hairpin of Rad4/XPC into the lesion siteand the flipping of CPD's partner bases (5'-dA and 3'-dA) are essential for damage recognition. Characterizing these slow events is challenging due to their infrequent occurrence on molecular time scales. Herein, we have used enhanced sampling and molecular dynamics simulations to investigate the mechanism and energetics of lesion recognition by Rad4/XPC, considering multiple plausible pathways between the crystal structure of the Rad4-DNA complex and nine intermediate states. Our results shed light on the most likely sequence of events, their potential coupling and energetics. Upon association, Rad4 and DNA form an encounter complex in which CPD and its partner bases remain in the duplex and the BHD3 β-hairpin is yet to be inserted into the lesion site. Subsequently, sequential base flipping occurs, with the flipping of the 5'-dA base preceding that of the 3'-dA base, followed by the insertion of the BHD3 β-hairpin into the lesion site. The results presented here have significant implications for understanding the molecular basis of UV-related skin disorders and cancers and for paving the way for novel therapeutic strategies.

How far can we stretch the timescale with RETIS?

Molecular dynamics (MD) and Monte Carlo (MC) have long coexisted as two main independent branches of molecular simulation. In the late eighties, however, algorithms based on the combination of both were created such as hybrid Monte Carlo which uses large MD steps as MC moves. An entirely different kind of combination emerged a decade later via the transition path sampling (TPS) method in which MD trajectories are not just part of the MC move, but also form the state space being sampled. Algorithms like replica exchange transition interface sampling (RETIS) exploit this idea to compute reaction rates via a series of TPS simulations. RETIS yields results identical to hypothetical long MD runs, but with exponentially reduced computation time. This perspective describes the RETIS method and discusses recent and future advancements that will enable the study of even longer molecular timescales with reasonable computational resources.

The evolutionary relationships of Diprotodontia and improving the accuracy of phylogenetic inference from morphological data

Large-scale molecular datasets have generally outperformed morphological data for inferring phylogeny, and sources of error in the latter are poorly understood. The morphologically and ecologically diverse marsupial order Diprotodontia (kangaroos and their relatives, the koala, wombats and possums) is well suited to considering these issues. Recent molecular results provide a phylogenetic benchmark for comparing previous molecular and morphological studies, encompassing all of the major phylogenetic data sources and methods that have been employed over the past 50 years. We show here that most molecular methodologies and ‘informal-comparative’ morphological studies have inferred diprotodontian relationships that closely resemble the recent molecular consensus. However, and perhaps surprisingly, algorithmic morphology, such as maximum parsimony analysis of morphological matrices, has inferred markedly inaccurate phylogenies, and is not improved by re-analysis with more recently developed, model-based (e.g., likelihood and Bayesian) methods. This is particularly concerning because algorithmic morphology is the primary approach for integrating fossils into the tree of life, and hence, for both calibrating molecular timescales and extending phylogenetic inferences of evolutionary processes beyond the snapshot provided by modern species. A novel simulation study presented here suggests that the inaccuracies in the marsupial algorithmic morphology studies partly stem from functional and body-size correlations among taxa that over-ride phylogenetic signals. We use the results to trial a reverse engineered phylogeny approach to correcting for such functional and developmental correlations among morphological data. In addition, we interrogated a newly published, densely taxon-sampled morphological matrix. Deeper level phylogeny reconstruction was improved by including fossils alongside extant taxa and counterintuitively, by increased effort to resolve relationships among shallow taxa.Matthew J. Phillips [m9.phillips@qut.edu.au]; Mélina A. Celik [melina.celik@gmail.com] School of Biology and Environmental Science, Queensland University of Technology, 2 George Street, Brisbane, Qld, 4000, Australia; Robin M.D Beck [r.m.d.beck@salford.ac.uk] Ecosystems and Environment Research Centre, School of Science, Engineering and Environment, University of Salford, Manchester, UK.

Development and Validation of Versatile Deep Atomistic Potentials for Metal Oxides.

Machine learning interatomic potentials powered by neural networks have been shown to readily model a gradient of compositions in metallic systems. However, their application to date on ionic systems tends to focus on specific compositions and oxidation states owing to their more heterogeneous chemical nature. Herein we show that a deep neural network potential (DNP) can model various properties of metal oxides with different oxidation states without additional charge information. We created and validated DNPs for AgxOy, CuxOy MgxOy, PtxOy, and ZnxOy, whereby each system was trained without any limitations on oxidation states. We illustrate how the database can be augmented to enhance the DNP transferability for a new polymorph, surface energies, and thermal expansion. In addition, we show that these potentials can correctly interpolate significant pressure and temperature ranges, exhibit stability over long molecular dynamics simulation time scales, and replicate nonharmonic thermal expansion, consistent with experimental results.

Ultrafast Spectroscopies of Nitrophenols and Nitrophenolates in Solution: From Electronic Dynamics and Vibrational Structures to Photochemical and Environmental Implications.

Nitrophenols are a group of small organic molecules with significant environmental implications from the atmosphere to waterways. In this work, we investigate a series of nitrophenols and nitrophenolates, with the contrasting ortho-, meta-, and para-substituted nitro group to the phenolic hydroxy or phenolate oxygen site (2/3/4NP or NP-), implementing a suite of steady-state and time-resolved spectroscopic techniques that include UV/Visible spectroscopy, femtosecond transient absorption (fs-TA) spectroscopy with probe-dependent and global analysis, and femtosecond stimulated Raman spectroscopy (FSRS), aided by quantum calculations. The excitation-dependent (400 and 267 nm) electronic dynamics in water and methanol, for six protonated or deprotonated nitrophenol molecules (three regioisomers in each set), enable a systematic investigation of the excited-state dynamics of these functional "nanomachines" that can undergo nitro-group twisting (as a rotor), excited-state intramolecular or intermolecular proton transfer (donor-acceptor, ESIPT, or ESPT), solvation, and cooling (chromophore) events on molecular timescales. In particular, the meta-substituted compound 3NP or 3NP- exhibits the strongest charge-transfer character with FSRS signatures (e.g., C-N peak frequency), and thus, does not favor nitroaromatic twist in the excited state, while the ortho-substituted compound 2NP can undergo ESIPT in water and likely generate nitrous acid (HONO) after 267 nm excitation. The delineated mechanistic insights into the nitro-substituent-location-, protonation-, solvent-, and excitation-wavelength-dependent effects on nitrophenols, in conjunction with the ultraviolet-light-induced degradation of 2NP in water, substantiates an appealing discovery loop to characterize and engineer functional molecules for environmental applications.

Analysis of Stress Relaxation in Bulk and Porous Ultra-High Molecular Weight Polyethylene (UHMWPE).

The reported study was devoted to the investigation of viscoelastic behavior for solid and porous ultra-high molecular weight polyethylene (UHMWPE) under compression. The obtained experimental stress curves were interpreted using a two-term Prony series to represent the superposition of two coexisting activation processes corresponding to long molecular (~160 s) and short structural (~20 s) time scales, respectively, leading to good statistical correlation with the observations. In the case of porous polymer, the internal strain redistribution during relaxation was quantified using digital image correlation (DIC) analysis. The strongly inhomogeneous deformation of the porous polymer was found not to affect the relaxation times. To illustrate the possibility of generalizing the results to three dimensions, X-ray tomography was used to examine the porous structure relaxation at the macro- and micro-scale levels. DIC analysis revealed positive correlation between the applied force and relative density. The apparent stiffness variation for UHMWPE foams with mixed open and closed cells was described using a newly proposed three-term expression. Furthermore, in situ tensile loading and X-ray scattering study was applied for isotropic solid UHMWPE specimens to investigate the evolution of internal structure and orientation during drawing and stress relaxation in another loading mode.

From Hidden Shear‐Elasticity to Opto‐ and Thermo‐Elastic Properties in Confined Polymer Melts and Viscous Liquids

AbstractThe newly identified low frequency elasticity of mesoscopic liquids opens the route to the identification of novel dynamic liquid properties. Two experimental examples illustrating the impact of the liquid elasticity in optics and thermodynamics are presented. It is revealed that at mesoscopic scale, liquids are able to convert the mechanical energy in optical and thermal effects. The fluids are submitted to a low frequency (∼Hz) mechanical shear strain (external stress), thus excluding a coupling with molecular time scales. The dynamic response is probed using two in situ methods accessing in real time optical response of the isotropic phase of liquid crystals and probing the thermal response upon shear deformation. In both cases, a dynamic response is identified: the isotropic phase of liquid crystals exhibits a low frequency dynamic birefringence while ordinary liquids exhibit cold and hot thermal waves synchronous to the low frequency excitation.

The greening ashore.

More than half a billion years ago a streptophyte algal lineage began terraforming the terrestrial habitat and the Earth's atmosphere. This pioneering step enabled the subsequent evolution of all complex life on land, and the past decade has uncovered that many traits, both morphological and genetic, once thought to be unique to land plants, are conserved across some streptophyte algae. They provided the common ancestor of land plants with a repertoire of genes, of which many were adapted to overcome the new biotic and abiotic challenges. Exploring these molecular adaptations in non-tracheophyte species may help us to better prepare all green life, including our crops, for the challenges precipitated by the climate change of the Anthropocene because the challenges mostly differ by the speed with which they are now being met.

Development of coarse-grained potential of silica species

ABSTRACT Understanding the molecular transformation of silica aggregates during silica polymerisation is crucial to control the properties of final products such as zeolite, nanoparticles, mesoporous silica and other polymorphs. Nevertheless, molecular events during synthesis are challenging to probe using experimental techniques. Computational tools are beneficial to probe molecular length and time scales; however, the complex systems with significant degrees of freedom require significant computational resources. In this work, we have developed coarse-grained (CG) potentials for silica system wherein every silica tetrahedron (Si(OH)O) having ‘z’ number of bridging oxygen is mapped to a unique CG silica bead (). Different composition of these CG silica beads represent a polymerised silica system with varying degrees of condensation. We performed molecular dynamics (MD) simulations of all-atom silica system to obtain reference radial distribution functions between various silica species (), which was used in Monte Carlo simulations of the CG system to obtain CG potentials. We iteratively refined the CG potentials using iterative Boltzmann inversion and inverse Monte Carlo techniques. We found two attractive minima in the CG potential between arising due to direct and indirect interactions of species representing first and second coordination shells. The strength of CG potential increases for both of minima with increasing number of bridging oxygen in species. We performed MD simulations of CG silica beads using developed CG potentials at two degree of condensations and found equilibrium structure of spherical silica nanoparticle. We found that and species are predominantly located at the centre of nanoparticles, whereas species are present uniformly.

Shear and Bulk Acceleration Viscosities in Simple Fluids.

Inhomogeneities in the velocity field of a moving fluid are dampened by the inherent viscous behavior of the system. Both bulk and shear effects, related to the divergence and the curl of the velocity field, are relevant. On molecular time scales, beyond the Navier-Stokes description, memory plays an important role. Using molecular and overdamped Brownian dynamics many-body simulations, we demonstrate that analogous viscous effects act on the acceleration field. This acceleration viscous behavior is associated with the divergence and the curl of the acceleration field, and it can be quantitatively described using simple exponentially decaying memory kernels. The simultaneous use of velocity and acceleration fields enables the description of fast dynamics on molecular scales.

Time resolved surface analysis (kinetic and molecular time scales): general discussion.

The first page of this article is displayed as the abstract.

The developmental biology of Charnia and the eumetazoan affinity of the Ediacaran rangeomorphs.

Molecular timescales estimate that early animal lineages diverged tens of millions of years before their earliest unequivocal fossil evidence. The Ediacaran macrobiota (~574 to 538 million years ago) are largely eschewed from this debate, primarily due to their extreme phylogenetic uncertainty, but remain germane. We characterize the development of Charnia masoni and establish the affinity of rangeomorphs, among the oldest and most enigmatic components of the Ediacaran macrobiota. We provide the first direct evidence for the internal interconnected nature of rangeomorphs and show that Charnia was constructed of repeated branches that derived successively from pre-existing branches. We find homology and rationalize morphogenesis between disparate rangeomorph taxa, before producing a phylogenetic analysis, resolving Charnia as a stem-eumetazoan and expanding the anatomical disparity of that group to include a long-extinct bodyplan. These data bring competing records of early animal evolution into closer agreement, reformulating our understanding of the evolutionary emergence of animal bodyplans.

The influence of upper boundary conditions on molecular kinetic atmospheric escape simulations

Molecular kinetic simulations are typically used to accurately describe the tenuous regions of the upper atmospheres on planetary bodies. These simulations track the motion of particles representing real atmospheric atoms and/or molecules subject to collisions, the object's gravity, and external influences. Because particles can end up in very large ballistic orbits, upper boundary conditions (UBC) are typically used to limit the domain size thereby reducing the time for the atmosphere to reach steady-state. In the absence of a clear altitude at which all molecules are removed, such as a Hill sphere, an often used condition is to choose an altitude at which collisions become infrequent so that particles on escape trajectories are removed. The remainder are then either specularly reflected back into the simulation domain or their ballistic trajectories are calculated analytically or explicitly tracked so they eventually re-enter the domain. Here we examine the effect of the choice of the UBC on the escape rate and the structure of the atmosphere near the nominal exobase in the convenient and frequently used 1D spherically symmetric approximation. Using Callisto as the example body, we show that the commonly used specular reflection UBC can lead to significant uncertainties when simulating a species with a lifetime comparable to or longer than a dynamical time scale, such as an overestimation of escape rates and an inflated exosphere. Therefore, although specular reflection is convenient, the molecular lifetimes and body's dynamical time scales need to be considered even when implementing the convenient 1D spherically symmetric simulations in order to accurately estimate the escape rate and the density and temperature structure in the transition regime.

Diversification dynamics of total-, stem-, and crown-groups are compatible with molecular clock estimates of divergence times.

Molecular evolutionary time scales are expected to predate the fossil evidence, but, particularly for major evolutionary radiations, they can imply extremely protracted stem lineages predating the origin of living clades, leading to claims of systematic overestimation of divergence times. We use macroevolutionary birth-death models to describe the range of total-group and crown-group ages expected under constant rates of speciation and extinction. We extend current predictions on origination times for crown- and total-groups, and extinction of stem-groups, demonstrating that there is broad variance in these predictions. Under constant rates of speciation and extinction, we show that the distribution of expected arthropod total-group ages is consistent with molecular clock estimates. The fossil record cannot be read literally, and our results preclude attempts to interpret the antiquity of clades based on the co-occurrence of stem- and crown-representatives.

Contribution to the taxonomic revision ofBrachycorythis-complex (Orchidaceae, Orchidoideae)

AbstractThe aim of this paper is to present materials towards the taxonomic revision ofBrachycorythis-complex (Orchidinae, Orchidaceae), which constitutes seven terrestrial genera and forty-eight species distributed in sub-Saharan Africa, Madagascar and SW Asia. The detailed morphological descriptions, together with distribution data and ecological preferences for particular taxa are provided. Artificial keys for taxa identification were prepared. A molecular timescale forBrachycorythisspecies on a background of the subtribe Orchidinae was reconstructed using nuclear and plastid molecular markers. The results show that representatives ofBrachycorythisseparated from its last common ancestor presumably ca 20 Mya and the youngest taxa within the group seem to be its Asiatic representatives.

An Engineered Biliverdin-Compatible Cyanobacteriochrome Enables a Unique Ultrafast Reversible Photoswitching Pathway

Cyanobacteriochromes (CBCRs) are promising optogenetic tools for their diverse absorption properties with a single compact cofactor-binding domain. We previously uncovered the ultrafast reversible photoswitching dynamics of a red/green photoreceptor AnPixJg2, which binds phycocyanobilin (PCB) that is unavailable in mammalian cells. Biliverdin (BV) is a mammalian cofactor with a similar structure to PCB but exhibits redder absorption. To improve the AnPixJg2 feasibility in mammalian applications, AnPixJg2_BV4 with only four mutations has been engineered to incorporate BV. Herein, we implemented femtosecond transient absorption (fs-TA) and ground state femtosecond stimulated Raman spectroscopy (GS-FSRS) to uncover transient electronic dynamics on molecular time scales and key structural motions responsible for the photoconversion of AnPixJg2_BV4 with PCB (Bpcb) and BV (Bbv) cofactors in comparison with the parent AnPixJg2 (Apcb). Bpcb adopts the same photoconversion scheme as Apcb, while BV4 mutations create a less bulky environment around the cofactor D ring that promotes a faster twist. The engineered Bbv employs a reversible clockwise/counterclockwise photoswitching that requires a two-step twist on ~5 and 35 picosecond (ps) time scales. The primary forward Pfr → Po transition displays equal amplitude weights between the two processes before reaching a conical intersection. In contrast, the primary reverse Po → Pfr transition shows a 2:1 weight ratio of the ~35 ps over 5 ps component, implying notable changes to the D-ring-twisting pathway. Moreover, we performed pre-resonance GS-FSRS and quantum calculations to identify the Bbv vibrational marker bands at ~659,797, and 1225 cm−1. These modes reveal a stronger H-bonding network around the BV cofactor A ring with BV4 mutations, corroborating the D-ring-dominant reversible photoswitching pathway in the excited state. Implementation of BV4 mutations in other PCB-binding GAF domains like AnPixJg4, AM1_1870g3, and NpF2164g5 could promote similar efficient reversible photoswitching for more directional bioimaging and optogenetic applications, and inspire other bioengineering advances.

Homogenous nucleation rate of CO2 hydrates using transition interface sampling.

Carbon dioxide and water can form solid clathrate structures in which water cages encapsulate the gas molecules. Such hydrates have sparked much interest due to their possible application in CO2 sequestration. How the solid structure forms exactly from the liquid phase via a homogenous nucleation process is still poorly understood. This nucleation event is rare on the molecular timescale even under moderate undercooling or supersaturation conditions because of the large free energy barrier toward crystallization, rendering a brute force simulation of hydrate nucleation unfeasible for moderate undercooling or supersaturation. Here, we perform transition interface sampling simulations to quantify the homogenous nucleation rate for CO2 hydrate formation using accurate atomistic force fields at 500 bars for three different temperatures between 260 and 273 K. Collecting more than 100 000 pathways comprising roughly two milliseconds of simulation time, we computed a nucleation rate in the amorphous phase of ∼1021 nuclei s-1 cm-3 for a temperature of 260 K and a rate of ∼1012 nuclei s-1 cm-3 for a temperature of 265 K. For a temperature of 273 K, we find that the hydrate forms an sI crystalline phase with a rate of order of ∼101 nuclei s-1 cm-3. We compare these rates to classical nucleation theory estimates as well as experiments, and to nucleation rate estimates for methane hydrates and discuss possible causes of the observed differences. Our findings shed light on the kinetics of this important clathrate and should assist in future hydrate formation investigation.