Polyply:A python suite for facilitating simulations of macromolecules and nanomaterials

Molecular dynamics simulations play an increasingly important role in the rational design of (nano)-materials and in the study of biomacromolecules. However, generating input files and realistic starting coordinates for these simulations is a major bottleneck, especially for high throughput protocols and for complex multi-component systems. To eliminate this bottleneck, we present the polyply software suite that provides 1) a multi-scale graph matching algorithm designed to generate parameters quickly and for arbitrarily complex polymeric topologies, and 2) a generic multi-scale random walk protocol capable of setting up complex systems efficiently and independent of the target force-field or model resolution. We benchmark quality and performance of the approach by creating realistic coordinates for polymer melt simulations, single-stranded as well as circular single-stranded DNA. We further demonstrate the power of our approach by setting up a microphase-separated block copolymer system, and by generating a liquid-liquid phase separated system inside a lipid vesicle

Divergent evolution of protein conformational dynamics in dihydrofolate reductase.

Molecular evolution is driven by mutations, which may affect the fitness of an organism and are then subject to natural selection or genetic drift. Analysis of primary protein sequences and tertiary structures has yielded valuable insights into the evolution of protein function, but little is known about the evolution of functional mechanisms, protein dynamics and conformational plasticity essential for activity. We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family. Despite structural similarity, Escherichia coli and human DHFRs use different dynamic mechanisms to perform the same function, and human DHFR cannot complement DHFR-deficient E. coli cells. Identification of the primary-sequence determinants of flexibility in DHFRs from several species allowed us to propose a likely scenario for the evolution of functionally important DHFR dynamics following a pattern of divergent evolution that is tuned by cellular environment

Stochastic Emergence of Two Distinct Self-Replicators from a Dynamic Combinatorial Library

[Image: see text] Unraveling how chemistry can give rise to biology is one of the greatest challenges of contemporary science. Achieving life-like properties in chemical systems is therefore a popular topic of research. Synthetic chemical systems are usually deterministic: the outcome is determined by the experimental conditions. In contrast, many phenomena that occur in nature are not deterministic but caused by random fluctuations (stochastic). Here, we report on how, from a mixture of two synthetic molecules, two different self-replicators emerge in a stochastic fashion. Under the same experimental conditions, the two self-replicators are formed in various ratios over several repeats of the experiment. We show that this variation is caused by a stochastic nucleation process and that this stochasticity is more pronounced close to a phase boundary. While stochastic nucleation processes are common in crystal growth and chiral symmetry breaking, it is unprecedented for systems of synthetic self-replicators

Quantitative dating of pleistocene deposits of the Kyrenia range, Northern Cyprus : implications for timing, rates of uplift and driving mechanisms

R.N.P. acknowledges the NERC CASE scholarship at the University of Edinburgh. Additional field and laboratory work was aided by the DARIUS Programme to A.H.F.R. and T.C.K. We are grateful for the additional financial support provided by the John Dixon Memorial Fund.The Kyrenia Range underwent tectonically driven uplift during the Pliocene to Pleistocene in response to the interaction of various tectonic processes. To understand the tectonic processes driving the uplift and how this is related to uplift of other areas of the Eastern Mediterranean, uranium-series disequilibrium and optically stimulated luminescence dating were applied to marine and non-marine terrace deposits exposed on the northern flank of the range. Palaeomagnetism and strontium isotope dating were used in conjunction to date the final stages of the marine environment adjacent to the Kyrenia Range prior to major surface uplift. Uplift rates range from >1.2 mm a−1, inferred during the Early Pleistocene, to <0.2 mm a−1during the Late Pleistocene. The new data show that the Kyrenia Range was uplifted contemporaneously with the Troodos Massif in southern Cyprus. The uplift of the Kyrenia Range appears to have been significantly faster than that affecting other comparable regions in the easternmost Mediterranean during the Pleistocene (e.g. Lebanon coast; southern Anatolian plateau). The driving mechanism for the uplift of both the Kyrenia Range and the Troodos Massif is inferred to be the collision of the Eratosthenes Seamount with the Cyprus trench to the south of Cyprus.Publisher PDFPeer reviewe

Bumpy black holes from spontaneous Lorentz violation

We consider black holes in Lorentz violating theories of massive gravity. We argue that in these theories black hole solutions are no longer universal and exhibit a large number of hairs. If they exist, these hairs probe the singularity inside the black hole providing a window into quantum gravity. The existence of these hairs can be tested by future gravitational wave observatories. We generically expect that the effects we discuss will be larger for the more massive black holes. In the simplest models the strength of the hairs is controlled by the same parameter that sets the mass of the graviton (tensor modes). Then the upper limit on this mass coming from the inferred gravitational radiation emitted by binary pulsars implies that hairs are likely to be suppressed for almost the entire mass range of the super-massive black holes in the centers of galaxies.Comment: 40 pages, 4 figure

Caught in the Act:Mechanistic Insight into Supramolecular Polymerization-Driven Self-Replication from Real-Time Visualization

Self-assembly features prominently in fields ranging from materials science to biophysical chemistry. Assembly pathways, often passing through transient intermediates, can control the outcome of assembly processes. Yet, the mechanisms of self-assembly remain largely obscure due to a lack of experimental tools for probing these pathways at the molecular level. Here, the self-assembly of self-replicators into fibers is visualized in real-time by high-speed atomic force microscopy (HS-AFM). Fiber growth requires the conversion of precursor molecules into six-membered macrocycles, which constitute the fibers. HS-AFM experiments, supported by molecular dynamics simulations, revealed that aggregates of precursor molecules accumulate at the sides of the fibers, which then diffuse to the fiber ends where growth takes place. This mechanism of precursor reservoir formation, followed by one-dimensional diffusion, which guides the precursor molecules to the sites of growth, reduces the entropic penalty associated with colocalizing precursors and growth sites and constitutes a new mechanism for supramolecular polymerization

An air-stable DPP-thieno-TTF copolymer for single-material solar cell devices and field effect transistors

Following an approach developed in our group to incorporate tetrathiafulvalene (TTF) units into conjugated polymeric systems, we have studied a low band gap polymer incorporating TTF as a donor component. This polymer is based on a fused thieno-TTF unit that enables the direct incorporation of the TTF unit into the polymer, and a second comonomer based on the diketopyrrolopyrrole (DPP) molecule. These units represent a donor–acceptor copolymer system, p(DPP-TTF), showing strong absorption in the UV–visible region of the spectrum. An optimized p(DPP-TTF) polymer organic field effect transistor and a single material organic solar cell device showed excellent performance with a hole mobility of up to 5.3 × 10–2 cm2/(V s) and a power conversion efficiency (PCE) of 0.3%, respectively. Bulk heterojunction organic photovoltaic devices of p(DPP-TTF) blended with phenyl-C71-butyric acid methyl ester (PC71BM) exhibited a PCE of 1.8%

Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates

Clinical epidemiolog

Two-year neurodevelopmental outcome in children born extremely preterm:the EPI-DAF study

OBJECTIVE: In 2010, the Dutch practice regarding initiation of active treatment in extremely preterm infants was lowered from 25 completed weeks' to 24 completed weeks' gestation. The nationwide Extremely Preterm Infants - Dutch Analysis on Follow-up Study was set up to provide up-to-date data on neurodevelopmental outcome at 2 years' corrected age (CA) after this guideline change. Design: National cohort study. PATIENTS: All live born infants between 240/7 weeks' and 266/7 weeks' gestational age who were 2 years' CA in 2018-2020. MAIN OUTCOME MEASURE: Impairment at 2 years' CA, based on cognitive score (Bayley-III-NL), neurological examination and neurosensory function. RESULTS: 651 of 991 live born infants (66%) survived to 2 years' CA, with data available for 554 (85%). Overall, 62% had no impairment, 29% mild impairment and 9% moderate-to-severe impairment (further defined as neurodevelopmental impairment, NDI). The percentage of survivors with NDI was comparable for infants born at 24 weeks', 25 weeks' and 26 weeks' gestation. After multivariable analysis, severe brain injury and low maternal education were associated with higher odds on NDI. NDI-free survival was 48%, 67% and 75% in neonatal intensive care unit (NICU)-admitted infants at 24, 25 and 26 weeks' gestation, respectively. CONCLUSIONS: Lowering the threshold has not been accompanied by a large increase in moderate-to-severely impaired infants. Among live-born and NICU-admitted infants, an increase in NDI-free survival was observed from 24 weeks' to 26 weeks' gestation. This description of a national cohort with high follow-up rates gives an accurate description of the range of outcomes that may occur after extremely preterm birth

Martini 3 : a general purpose force field for coarse-grained molecular dynamics

The coarse-grained Martini force field is widely used in biomolecular simulations. Here we present the refined model, Martini 3 (http://cgmartini.nl), with an improved interaction balance, new bead types and expanded ability to include specific interactions representing, for example, hydrogen bonding and electronic polarizability. The updated model allows more accurate predictions of molecular packing and interactions in general, which is exemplified with a vast and diverse set of applications, ranging from oil/water partitioning and miscibility data to complex molecular systems, involving protein-protein and protein-lipid interactions and material science applications as ionic liquids and aedamers.Peer reviewe