A multi-modal coarse grained model of DNA flexibility mappable to the atomistic level.

We present a new coarse grained method for the simulation of duplex DNA. The algorithm uses a generalized multi-harmonic model that can represent any multi-normal distribution of helical parameters, thus avoiding caveats of current mesoscopic models for DNA simulation and representing a breakthrough in the field. The method has been parameterized from accurate parmbsc1 atomistic molecular dynamics simulations of all unique tetranucleotide sequences of DNA embedded in long duplexes and takes advantage of the correlation between helical states and backbone configurations to derive atomistic representations of DNA. The algorithm, which is implemented in a simple web interface and in a standalone package reproduces with high computational efficiency the structural landscape of long segments of DNA untreatable by atomistic molecular dynamics simulations.

Modulation of the helical properties of DNA: next-to-nearest neighbour effects and beyond.

We used extensive molecular dynamics simulations to study the structural and dynamic properties of the central d(TpA) step in the highly polymorphic d(CpTpApG) tetranucleotide. Contrary to the assumption of the dinucleotide-model and its nearest neighbours (tetranucleotide-model), the properties of the central d(TpA) step change quite significantly dependent on the next-to-nearest (hexanucleotide) sequence context and in a few cases are modulated by even remote neighbours (beyond next-to-nearest from the central TpA). Our results highlight the existence of previously undescribed dynamical mechanisms for the transmission of structural information into the DNA and demonstrate the existence of certain sequences with special physical properties that can impact on the global DNA structure and dynamics.

The static and dynamic structural heterogeneities of B-DNA: extending Calladine-Dickerson rules.

We present a multi-laboratory effort to describe the structural and dynamical properties of duplex B-DNA under physiological conditions. By processing a large amount of atomistic molecular dynamics simulations, we determine the sequence-dependent structural properties of DNA as expressed in the equilibrium distribution of its stochastic dynamics. Our analysis includes a study of first and second moments of the equilibrium distribution, which can be accurately captured by a harmonic model, but with nonlocal sequence-dependence. We characterize the sequence-dependent choreography of backbone and base movements modulating the non-Gaussian or anharmonic effects manifested in the higher moments of the dynamics of the duplex when sampling the equilibrium distribution. Contrary to prior assumptions, such anharmonic deformations are not rare in DNA and can play a significant role in determining DNA conformation within complexes. Polymorphisms in helical geometries are particularly prevalent for certain tetranucleotide sequence contexts and are always coupled to a complex network of coordinated changes in the backbone. The analysis of our simulations, which contain instances of all tetranucleotide sequences, allow us to extend Calladine-Dickerson rules used for decades to interpret the average geometry of DNA, leading to a set of rules with quantitative predictive power that encompass nonlocal sequence-dependence and anharmonic fluctuations.

Allosterism and signal transfer in DNA.

We analysed the basic mechanisms of signal transmission in DNA and the origins of the allostery exhibited by systems such as the ternary complex BAMHI-DNA-GRDBD. We found that perturbation information generated by a primary protein binding event travels as a wave to distant regions of DNA following a hopping mechanism. However, such a structural perturbation is transient and does not lead to permanent changes in the DNA geometry and interaction properties at the secondary binding site. The BAMHI-DNA-GRDBD allosteric mechanism does not occur through any traditional models: direct (protein-protein), indirect (reorganization of the secondary site) readout or solvent-release. On the contrary, it is generated by a subtle and less common entropy-mediated mechanism, which might have an important role to explain other DNA-mediated cooperative effects.

Parmbsc1: a refined force field for DNA simulations.

We present parmbsc1, a force field for DNA atomistic simulation, which has been parameterized from high-level quantum mechanical data and tested for nearly 100 systems (representing a total simulation time of ∼ 140 µs) covering most of DNA structural space. Parmbsc1 provides high-quality results in diverse systems. Parameters and trajectories are available at http://mmb.irbbarcelona.org/ParmBSC1/.

How to engineer glucose oxidase for mediated electron transfer.

Glucose oxidase (GOx) is of high industrial interest for glucose sensing because of its high ß-d-glucose specificity. The efficient and specific electrochemical communication between the redox center and electrodes is crucial to ensure accurate glucose determination. The efficiency of the electron transfer rates (ETR) with GOx, together with quinone diamine based mediators, is low and differs even among mediator derivatives. To design optimized enzyme-mediator couples and to describe a mediator binding model, a joint experimental and computational study was performed based on an oxygen-independent GOx variant V7 and two quinone diimine based electron mediators (QDM-1 and QDM-2), which differ in polarity and size, and ferrocenemethanol (FM). A site saturation library at position 414 was screened with all three mediators and yielded four beneficial substitutions Tyr, Met, Leu, and Val. The variants showed increased mediator activity for the more polar QDM-2 with a simultaneously decreased activity for the less polar and smaller QDM-1 and for FM. The variant GOx V7-I414Y exhibited the biggest change for the quinone diimine derivatives compared with V7 (QDM-1: 55.9 U/mg V7, 33.2 U/mg V7-I414Y; QDM-2: 2.7 U/mg V7, 12.9 U/mg V7-I414Y). Theoretical ETR calculated based on the Marcus theory were in good agreement with the experimental results. Molecular docking studies revealed a preferable binding of the two QD mediators directly in the active site, 3.5 Å away from the N5 atom of the flavin adenine dinucleotide (FAD) and in direct vicinity to position 414. In summary, position 414 in the active site was identified to modulate the electron shuttling from the FAD of the GOx to small water-soluble mediators dependent on the polarity and size of residue 414 and on the polarity and size of the mediator. The presented mediator binding model offers a promising possibility for the design of optimized enzyme-mediator couples.

How to Increase Employees' Proactive Vitality Management? Testing the Effect of a Training Intervention.

Drawing on the Job Demands-Resources theory, we investigate the effectiveness of an online intervention based on training in energy management strategies using an experimental design. The intervention focused on creating awareness about the importance of energy in completing tasks, shaping the present state, and proactively identifying valuable strategies to manage vitality during work. Additionally, we expected an increase in work-related strategies (i.e., setting a new goal) and a decrease in micro-breaks (i.e., mental and physical). Participants were enrolled voluntarily in the intervention and randomly assigned to the experimental group (N = 42) and the control group (N = 44). Results of the ANCOVA showed that, in the experimental group, the intervention positively impacted changes in proactive vitality management. Furthermore, the results indicated that the participants from the experimental group used fewer physical micro-breaks after the intervention. Additionally, after the training and weekly level, the results showed a decrease in work-related strategies and physical micro-breaks in the experimental group. Thus, organizations could facilitate employees to learn to engage in different energy management strategies according to their preferences.

Psychometric Evaluation of the Proactive Vitality Management Scale: Invariance, Convergent, and Discriminant Validity of the Romanian Version.

The present research aims to evaluate the psychometric properties of the Romanian version of the Proactive Vitality Management (PVM) scale. Based on the Job Demands-Resources theory, PVM is a proactive behavior that helps employees manage energy at work. Two studies were conducted to test the reliability and validity of the PVM scale. The first study (N = 477) aimed to validate the Romanian version of PVM and test for measurement invariance related to gender. The results of the confirmatory factor analysis indicated a one-factor model and good values of the fit indices. Moreover, the indicators of measurement invariance showed no difference between men and women; both groups interpret the measure in a conceptually similar way. The second study (N = 307) cross-validated the one-factor model, tested discriminant and criterion validity between PVM and other constructs, such as psychological detachment and well-being (e.g., work engagement, health). The results indicated that PVM is indeed a one-factor construct associated with well-being indicators and unrelated to psychological detachment. From a practical perspective, the PVM scale is a reliable and valid instrument for assessing proactive energy management in organizations and developing strategies and interventions for employees to function optimally and reach their work-related well-being. The study also provides evidence of the PVM in the Job Demands-Resources theory as a proactive behavior at work, which represents a new strategy for employees to function optimally at work by deciding when and how to manage their energy.

Feedback-Seeking Behavior in Organizations: A Meta-Analysis and Systematical Review of Longitudinal Studies.

Based on the Job Demands-Resources theory, this meta-analysis investigates the role of resources in predicting feedback-seeking behavior (FSB) over time. We also examine the relationship between FSB and its outcomes from a systematic review perspective. The eligibility criteria were: (a) to measure feedback-seeking behavior, (b) to have a longitudinal design, and (c) to have employees as target groups. Thirteen studies met these criteria (Ntotal= 1,527). We combined the meta-analysis procedures and structural equation modeling (metaSEM) and used the systematic review. The methodological quality of the available longitudinal studies is assessed. Our findings indicated that job resources predict future feedback-seeking behavior and between feedback-seeking behavior and personal resources is significant relationship. More research is needed to clarify the reciprocal relationships between personal resources and feedback-seeking behavior and the influences of feedback-seeking behavior on performance.

An immune receptor complex evolved in soybean to perceive a polymorphic bacterial flagellin.

In both animals and plants, the perception of bacterial flagella by immune receptors elicits the activation of defence responses. Most plants are able to perceive the highly conserved epitope flg22 from flagellin, the main flagellar protein, from most bacterial species. However, flagellin from Ralstonia solanacearum, the causal agent of the bacterial wilt disease, presents a polymorphic flg22 sequence (flg22Rso) that avoids perception by all plants studied to date. In this work, we show that soybean has developed polymorphic versions of the flg22 receptors that are able to perceive flg22Rso. Furthermore, we identify key residues responsible for both the evasion of perception by flg22Rso in Arabidopsis and the gain of perception by the soybean receptors. Heterologous expression of the soybean flg22 receptors in susceptible plant species, such as tomato, enhances resistance to bacterial wilt disease, demonstrating the potential of these receptors to enhance disease resistance in crop plants.

The Role of Unconventional Hydrogen Bonds in Determining BII Propensities in B-DNA.

An accurate understanding of DNA backbone transitions is likely to be the key for elucidating the puzzle of the intricate sequence-dependent mechanical properties that govern most of the biologically relevant functions of the double helix. One factor believed to be important in indirect recognition within protein-DNA complexes is the combined effect of two DNA backbone torsions (ε and ζ) which give rise to the well-known BI/BII conformational equilibrium. In this work we explain the sequence-dependent BII propensity observed in RpY steps (R = purine; Y = pyrimidine) at the tetranucleotide level with the help of a previously undetected C-H···O contact between atoms belonging to adjacent bases. Our results are supported by extensive multimicrosecond molecular dynamics simulations from the Ascona B-DNA Consortium, high-level quantum mechanical calculations, and data mining of the experimental structures deposited in the Protein Data Bank.