Toy System Research Articles

Alchemical Metadynamics: Adding Alchemical Variables to Metadynamics to Enhance Sampling in Free Energy Calculations.

Performing alchemical transformations, in which one molecular system is nonphysically changed to another system, is a popular approach adopted in performing free energy calculations associated with various biophysical processes, such as protein-ligand binding or the transfer of a molecule between environments. While the sampling of alchemical intermediate states in either parallel (e.g., Hamiltonian replica exchange) or serial manner (e.g., expanded ensemble) can bridge the high-probability regions in the configurational space between two end states of interest, alchemical methods can fail in scenarios where the most important slow degrees of freedom in the configurational space are, in large part, orthogonal to the alchemical variable, or if the system gets trapped in a deep basin extending in both the configurational and alchemical space. To alleviate these issues, we propose to use alchemical variables as an additional dimension in metadynamics, making it possible to both sample collective variables and to enhance sampling in free energy calculations simultaneously. In this study, we validate our implementation of "alchemical metadynamics" in PLUMED with test systems and alchemical processes with varying complexities and dimensionalities of collective variable space, including the interconversion between the torsional metastable states of a toy system and the methylation of a nucleoside both in the isolated form and in a duplex. We show that multidimensional alchemical metadynamics can address the challenges mentioned above and further accelerate sampling by introducing configurational collective variables. The method can trivially be combined with other metadynamics-based algorithms implemented in PLUMED. The necessary PLUMED code changes have already been released for general use in PLUMED 2.8.

Atomic Group Decomposition of Charge Transfer Excitation Global Indexes.

A model for decomposing the Le Bahers, Adamo, and Ciofini Charge Transfer (CT) Excitations global indexes (J. Chem. Theory Comput.2011, 7, 2498−250626606624) into molecular subdomains contributions is presented and a software, DOCTRINE (atomic group Decomposition Of the Charge TRansfer INdExes) for the implementation of this novel model has been coded. Although our method applies to any fuzzy or to any disjoint exhaustive partitioning of the real space, it is here applied using a definition of chemically relevant molecular subdomains based on the Atoms in Molecules Bader basins. This choice has the relevant advantage of associating intra or inter subdomain contributions to rigorously defined quantum objects, yet bearing a clear chemical meaning. Our method allows for a quantitative evaluation of the subdomain contributions to the charge transfer, the charge transfer excitation length and the dipole moment change upon excitation. All these global indexes may be obtained either from the electron density increment or the electron density depletion upon excitation. However, the subdomain contributions obtained from the two distributions generally differ, therefore allowing to distinguish whether the contribution to a given property of a given subdomain is dominated by one of the two distributions or if both are playing a significant role. As a toy system for the first application of our model, a typical [D−π–A, π = conjugated bridge] compound belonging to the merocyanine dyes family is selected, and the first four excited states of this compound in a strongly polar protic solvent and in a weakly polar solvent are thoroughly investigated.

The playful unliving: Creativity and contingency in scientific practice

Standing apart from Martin Heidegger’s 1929–1930 metaphysical lessons is his description of a photograph taken by Josef Maria Eder, for Sigmund Exner, using the lens of a glow worm’s eye. Since the technical details of the production of such a photography are not readily available, I will reconstruct the experimental setting. Paying attention to the technical details opens up a venue for historical and philosophical reflection based on the creative potential of scientific practices. Through a critical approach, a rather generic experimental meshwork could be turned into a natural-artifactual, living-nonliving hybrid setting in which the concepts of dense technological environment, philosophical toy, and experimental system meet and intertwine thanks to the playfulness that goes through them, a quality rooted in scientific practices. Within this hybrid and playful configuration, the unliving emerges as a paradoxical voice for the living.

A wooden toy design method based on the educational toy system

A wooden toy design method based on the educational toy system

Extrapolation and interpolation strategies for efficiently estimating structural observables as a function of temperature and density.

Thermodynamic extrapolation has previously been used to predict arbitrary structural observables in molecular simulations at temperatures (or relative chemical potentials in open-system mixtures) different from those at which the simulation was performed. This greatly reduces the computational cost in mapping out phase and structural transitions. In this work, we explore the limitations and accuracy of thermodynamic extrapolation applied to water, where qualitative shifts from anomalous to simple-fluid-like behavior are manifested through shifts in the liquid structure that occur as a function of both temperature and density. We present formulas for extrapolating in volume for canonical ensembles and demonstrate that linear extrapolations of water's structural properties are only accurate over a limited density range. On the other hand, linear extrapolation in temperature can be accurate across the entire liquid state. We contrast these extrapolations with classical perturbation theory techniques, which are more conservative and slowly converging. Indeed, we show that such behavior is expected by demonstrating exact relationships between extrapolation of free energies and well-known techniques to predict free energy differences. An ideal gas in an external field is also studied to more clearly explain these results for a toy system with fully analytical solutions. We also present a recursive interpolation strategy for predicting arbitrary structural properties of molecular fluids over a predefined range of state conditions, demonstrating its success in mapping qualitative shifts in water structure with density.

Machine learning the computational cost of quantum chemistry

Computational quantum mechanics based molecular and materials design campaigns consume increasingly more high-performance computer resources, making improved job scheduling efficiency desirable in order to reduce carbon footprint or wasteful spending. We introduce quantum machine learning (QML) models of the computational cost of common quantum chemistry tasks. For 2D nonlinear toy systems, single point, geometry optimization, and transition state calculations the out of sample prediction error of QML models of wall times decays systematically with training set size. We present numerical evidence for a toy system containing two functions and three commonly used optimizer and for thousands of organic molecular systems including closed and open shell equilibrium structures, as well as transition states. Levels of electronic structure theory considered include B3LYP/def2-TZVP, MP2/6-311G(d), local CCSD(T)/VTZ-F12, CASSCF/VDZ-F12, and MRCISD+Q-F12/VDZ-F12. In comparison to conventional indiscriminate job treatment, QML based wall time predictions significantly improve job scheduling efficiency for all tasks after training on just thousands of molecules. Resulting reductions in CPU time overhead range from 10% to 90%.

Stopping light using a transient Bragg grating

We employ a recently developed optical pulse propagation formulation suitable for slow and stopped light regimes to demonstrate light stopping by a (transient) grating coupling in a toy system, which is, however, applicable to a range of wave systems. We study the complete spatiotemporal dynamics, the characteristic timescales, the coupling efficiencies, and the spectral contents of the stopped pulse. Finally, we demonstrate numerically a delay line which surpasses the delay-bandwidth limit.

Design and Implementation of Visible Light Communication based toys

This paper presents the design and implementation steps of a smart visible light communication based toy system equipped with laser sensors that can send and receive the data message based on the conversion of data from ASCII to binary code. The toy system intends to offer two-ways communication that will be a new medium for educational purposes for kids in their developmental stages in which both players can send and receive the data to and from each other toys equipped with sound indicator module to alert the player. Lastly, functionality and system testing were conducted to verify the functionalities of the system. A thorough implementation methodology details are presented in the paper.

Deflation reveals dynamical structure in nondominant reaction coordinates

The output of molecular dynamics simulations is high-dimensional, and the degrees of freedom among the atoms are related in intricate ways. Therefore, a variety of analysis frameworks have been introduced in order to distill complex motions into lower-dimensional representations that model the system dynamics. These dynamical models have been developed to optimally approximate the system’s global kinetics. However, the separate aims of optimizing global kinetics and modeling a process of interest diverge when the process of interest is not the slowest process in the system. Here, we introduce deflation into state-of-the-art methods in molecular kinetics in order to preserve the use of variational optimization tools when the slowest dynamical mode is not the same as the one we seek to model and understand. First, we showcase deflation for a simple toy system and introduce the deflated variational approach to Markov processes (dVAMP). Using dVAMP, we show that nondominant reaction coordinates produced using deflation are more informative than their counterparts generated without deflation. Then, we examine a protein folding system in which the slowest dynamical mode is not folding. Following a dVAMP analysis, we show that deflation can be used to obscure this undesired slow process from a kinetic model; in this case, a VAMPnet. The incorporation of deflation into current methods opens the door for enhanced sampling strategies and more flexible, targeted model building.

Basma: An Interactive IoT-Based Plush Toy for Arabic-Speaking Children

A toy is an item mainly intended for children to play with. However, due to its important role in child development, it has evolved to encompass sophisticated educational and learning characteristics. Toy industry has evolved to provide these needs as digital interactive smart toys. Interactive toys combine traditional toys with additional computing capabilities using software and hardware components. This paper presents the design and development of an interactive toy system named “Basma” which interacts with a child in Arabic language. The system consists of two parts: The first one is a plush toy with a hardware component that is implemented using a low cost Internet of Things (IoT) kit. This part leverages the interaction between the child and the toy, allowing the toy to respond and talk. The second part is an iPad application connected to the toy via Bluetooth. It allows parents to customize the toy and provides the child with stories that embed moral and cultural values. The interactive toy system was evaluated using test scenarios and user acceptance.

Detection of unstable periodic orbits in mineralising geological systems.

Worldwide, mineral exploration is suffering from rising capital costs, due to the depletion of readily recoverable reserves and the need to discover and assess more inaccessible or geologically complex deposits. For gold exploration, this problem is particularly acute. We propose an innovative approach to mineral exploration and orebody characterisation, based on the analysis of geological core data as a spatial dynamical system, using the mathematical tools of dynamical system analysis. This approach is highly relevant for orogenic gold deposits, which-in contrast to systems formed at chemical equilibrium-exhibit many features of nonlinear dynamical systems, including episodic fluctuations on various length and time scales. Feedback relationships between thermo-chemical and deformation processes produce recurrent fluid temperatures and pressures and the deposition of vein-filling minerals such as pyrite and gold. We therefore relax the typical assumption of chemical equilibrium and analyse the underlying processes as aseismic, non-adiabatic, and inherent to a hydrothermal, nonlinear dynamical open-flow chemical reactor. These processes are approximated using the Gray-Scott model of reaction-diffusion as a complex toy system, which captures some of the features of the underlying mineralisation processes, including the spatiotemporal Turing patterns of unsteady chemical reactions. By use of this analysis, we demonstrate the capability of recurrence plots, recurrence power spectra, and recurrence time probabilities to detect underlying unstable periodic orbits as one sign of deterministic dynamics and their robustness for the analysis of data contaminated by noise. Recurrence plot based quantification is then applied to three mineral concentrations in the core data from the Sunrise Dam gold deposit in the Yilgarn region of Western Australia. Using a moving window, we reveal the episodic recurring low-dimensional dynamic structures and the period doubling route to instability with depth, embedded in and originating from higher-dimensional processes of the complex mineralisation system.

Energy decay in a tapped granular column: Can a one-dimensional toy model provide insight into fully three-dimensional systems?

The decay of energy within particulate media subjected to an impulse is an issue of significant scientific interest, but also one with numerous important practical applications. In this paper, we study the dynamics of a granular system exposed to energetic impulses in the form of discrete taps from a solid surface. By considering a one-dimensional toy system, we develop a simple theory, which successfully describes the energy decay within the system following exposure to an impulse. We then extend this theory so as to make it applicable also to more realistic, three-dimensional granular systems, assessing the validity of the model through direct comparison with discrete particle method simulations. The theoretical form presented possesses several notable consequences; in particular, it is demonstrated that for suitably large systems, effects due to the bounding walls may be entirely neglected. We also establish the existence of a threshold system size above which a granular bed may be considered fully three dimensional.

Smart Toys Designed for Detecting Developmental Delays.

In this paper, we describe the design considerations and implementation of a smart toy system, a technology for supporting the automatic recording and analysis for detecting developmental delays recognition when children play using the smart toy. To achieve this goal, we take advantage of the current commercial sensor features (reliability, low consumption, easy integration, etc.) to develop a series of sensor-based low-cost devices. Specifically, our prototype system consists of a tower of cubes augmented with wireless sensing capabilities and a mobile computing platform that collect the information sent from the cubes allowing the later analysis by childhood development professionals in order to verify a normal behaviour or to detect a potential disorder. This paper presents the requirements of the toy and discusses our choices in toy design, technology used, selected sensors, process to gather data from the sensors and generate information that will help in the decision-making and communication of the information to the collector system. In addition, we also describe the play activities the system supports.

Two Relations to Estimate Membrane Permeability Using Milestoning.

Prediction of passive permeation rates of solutes across lipid bilayers is important to drug design, toxicology, and other biological processes such as signaling. The inhomogeneous solubility-diffusion (ISD) equation is traditionally used to relate the position-dependent potential of mean force and diffusivity to the permeability coefficient. The ISD equation is derived via the Smoluchowski equation and assumes overdamped system dynamics. It has been suggested that the complex membrane environment may exhibit more complicated damping conditions. Here we derive a variant of the inhomogeneous solubility diffusion equation as a function of the mean first passage time (MFPT) and show how milestoning, a method that can estimate kinetic quantities of interest, can be used to estimate the MFPT of membrane crossing and, by extension, the permeability coefficient. We further describe a second scheme, agnostic to the damping condition, to estimate the permeability coefficient from milestoning results or other methods that compute a probability of membrane crossing. The derived relationships are tested using a one-dimensional Langevin dynamics toy system confirming that the presented theoretical methods can be used to estimate permeabilities given simulation and milestoning results.

Resolution-of-identity stochastic time-dependent configuration interaction for dissipative electron dynamics in strong fields.

In this contribution, we introduce a method for simulating dissipative, ultrafast many-electron dynamics in intense laser fields. The method is based on the norm-conserving stochastic unraveling of the dissipative Liouville-von Neumann equation in its Lindblad form. The N-electron wave functions sampling the density matrix are represented in the basis of singly excited configuration state functions. The interaction with an external laser field is treated variationally and the response of the electronic density is included to all orders in this basis. The coupling to an external environment is included via relaxation operators inducing transition between the configuration state functions. Single electron ionization is represented by irreversible transition operators from the ionizing states to an auxiliary continuum state. The method finds its efficiency in the representation of the operators in the interaction picture, where the resolution-of-identity is used to reduce the size of the Hamiltonian eigenstate basis. The zeroth-order eigenstates can be obtained either at the configuration interaction singles level or from a time-dependent density functional theory reference calculation. The latter offers an alternative to explicitly time-dependent density functional theory which has the advantage of remaining strictly valid for strong field excitations while improving the description of the correlation as compared to configuration interaction singles. The method is tested on a well-characterized toy system, the excitation of the low-lying charge transfer state in LiCN.

Revealing electronic open quantum systems with subsystem TDDFT.

Open quantum systems (OQSs) are perhaps the most realistic systems one can approach through simulations. In recent years, describing OQSs with Density Functional Theory (DFT) has been a prominent avenue of research with most approaches based on a density matrix partitioning in conjunction with an ad-hoc description of system-bath interactions. We propose a different theoretical approach to OQSs based on partitioning of the electron density. Employing the machinery of subsystem DFT (and its time-dependent extension), we provide a novel way of isolating and analyzing the various terms contributing to the coupling between the system and the surrounding bath. To illustrate the theory, we provide numerical simulations on a toy system (a molecular dimer) and on a condensed phase system (solvated excimer). The simulations show that non-Markovian dynamics in the electronic system-bath interactions are important in chemical applications. For instance, we show that the superexchange mechanism of transport in donor-bridge-acceptor systems is a non-Markovian interaction between the donor-acceptor (OQS) with the bridge (bath) which is fully characterized by real-time subsystem time-dependent DFT.

Designing mechanical complexity

Physics![Figure][1] Mechanical pendulasIMAGE: HEIDI HOSTETTLER The quantum properties of topological insulators translate to mechanical systems governed by Newton's equations of motion. Many-body interactions and the multiple degrees of freedom available to charge carriers give electronic systems a range of exotic behaviors. Susstrunk and Huber show that this extends to mechanical systems made up of a large lattice of coupled pendula. Mechanical excitations can be eliminated from the inner part of the lattice and confined to the edges, much like topological insulators. In addition to presenting a tractable toy system in which to study complex phenomena, the approach has potential uses in vibration isolation. Science , this issue p. [47][2] [1]: pending:yes [2]: /lookup/doi/10.1126/science.aab0239

Toward New Solvents for EDLCs: From Computational Screening to Electrochemical Validation

The development of innovative electrolytes is a key aspect of improving electrochemical double layer capacitors (EDLCs). New solvents, new conducting salts as well as new ionic liquids need to be considered. To avoid time-consuming “trial and error” experiments, it is desirable to “rationalize” this search for new materials. An important step in this direction is the systematic application of computational screening approaches. Via the fast prediction of the properties of a large number of compounds, for instance all reasonable candidates within a given compound class, such approaches should allow to identify of the most promising candidates for subsequent experiments. In this work we consider the toy system of all reasonable nitrile solvents up to 12 heavy atoms. To investigate if our recently proposed computational screening strategy is a feasible tool for the purpose of rationalizing the search for new EDLC electrolyte materials, we correlate—in the case of EDLCs for the first time—computational screen...

Quantifying Macromolecular Conformational Transition Pathways

Diverse classes of proteins such as molecular motors, enzymes, and active transmembrane transporters function through large-scale conformational changes. Computer simulations of these conformational transitions are challenging. A range of coarse-grained and biased simulation techniques have been used to generate individual transitions or ensembles of transition pathways but it has been difficult to compare pathways produced by different methods and so to assess their relative strengths. We introduce a comprehensive method (pathway similarity analysis, PSA) for quantitatively characterizing and comparing macromolecular pathways. The Hausdorff and Frechet metrics (known from computational geometry) are used to quantify the degree of similarity between piecewise-linear curves in configuration space. We tested PSA on a toy system to study the effect of temperature fluctuations (path roughness) and dimensionality. We compare a sample of publicly accessible transition pathway simulation servers and our own dynamic importance sampling (DIMS) MD method for the closed-to-open transitions of the apo enzyme adenylate kinase (AdK). PSA was applied to ensembles of hundreds of trajectories of the conformational transitions of the transporter Mhp1 and of AdK and diphtheria toxin, which were produced by DIMS MD and the Geometrical Pathways algorithm. Clustered PSA enabled the selection of a small subset of representative trajectories for further analysis. A strength of PSA is its use of the full information available from the 3N-dimensional configuration space trajectory, without requiring additional specific knowledge about the system. We show how trajectory analysis methods relying on pre-defined collective variables such as native contacts or geometric quantities can be used synergistically with PSA. We discuss the method's potential to enhance our understanding of transition path sampling methods, validate them, and ultimately help guide future research toward deeper physical insights into conformational transitions.

Transition path sampling with quantum/classical mechanics for reaction rates.

Predicting rates of biochemical reactions through molecular simulations poses a particular challenge for two reasons. First, the process involves bond formation and/or cleavage and thus requires a quantum mechanical (QM) treatment of the reaction center, which can be combined with a more efficient molecular mechanical (MM) description for the remainder of the system, resulting in a QM/MM approach. Second, reaction time scales are typically many orders of magnitude larger than the (sub-)nanosecond scale accessible by QM/MM simulations. Transition path sampling (TPS) allows to efficiently sample the space of dynamic trajectories from the reactant to the product state without an additional biasing potential. We outline here the application of TPS and QM/MM to calculate rates for biochemical reactions, by means of a simple toy system. In a step-by-step protocol, we specifically refer to our implementation within the MD suite Gromacs, which we have made available to the research community, and include practical advice on the choice of parameters.