General Force Research Articles

Development and test of highly accurate endpoint free energy methods. 2: Prediction of logarithm of n-octanol-water partition coefficient (logP) for druglike molecules using MM-PBSA method.

The logarithm of n-octanol-water partition coefficient (logP) is frequently used as an indicator of lipophilicity in drug discovery, which has substantial impacts on the absorption, distribution, metabolism, excretion, and toxicity of a drug candidate. Considering that the experimental measurement of the property is costly and time-consuming, it is of great importance to develop reliable prediction models for logP. In this study, we developed a transfer free energy-based logP prediction model-FElogP. FElogP is based on the simple principle that logP is determined by the free energy change of transferring a molecule from water to n-octanol. The underlying physical method to calculate transfer free energy is the molecular mechanics-Poisson Boltzmann surface area (MM-PBSA), thus this method is named as free energy-based logP (FElogP). The superiority of FElogP model was validated by a large set of 707 structurally diverse molecules in the ZINC database for which the measurement was of high quality. Encouragingly, FElogP outperformed several commonly-used QSPR or machine learning-based logP models, as well as some continuum solvation model-based methods. The root-mean-square error (RMSE) and Pearson correlation coefficient(R) between the predicted and measured values are 0.91 log units and 0.71, respectively, while the runner-up, the logP model implemented in OpenBabel had an RMSE of 1.13 log units and R of 0.67. Given the fact that FElogP was not parameterized against experimental logP directly, its excellent performance is likely to be expanded to arbitrary organic molecules covered by the general AMBER force fields.

GAFF-AIC: reoptimisation of the GAFF force field for realistic densities and viscosities in aromatic isocyanates

ABSTRACT Molecular mechanical force field methods, which help to investigate material properties beyond molecular scales, describe the intra- and intermolecular interactions of molecules assuming a classical force field comprised of several terms. Force fields should accurately describe the energy interactions of all moleculer elements to, eventually, accurately reproduce macromolecular properties of that materials. In the case of aromatic isocyanates, general purpose force fields failed to properly account for molecular interactions and, consequently, at the prediction of macromolecular properties of isocyanate-based materials. The present study presents a new force field based on the General AMBER Force Field (GAFF), namely GAFF-AIC, which shows improved results for the prediction of macromolecular properties, in particular density and viscosities, of materials based on aromatic isocyanates. For that, a new set of parameters for intramolecular and intermolecular interactions has been optimised by means of a least square fitting. It is shown that GAFF-AIC is able to accurately reproduce the experimental density and viscosity of liquid 1-naphtyl isocyanate. Moreover, these newly proposed force field parameters were evaluated to see how efficient they were at predicting the liquid densities and viscosities for several considered aromatic isocyanates, resulting in an accurate estimation that is in excellent agreement with experimental results.

Molecular Dynamics Simulation of Adsorption and Absorption Behavior of Shale Oil in Realistic Kerogen Slits

Exploring the occurrence of shale oil is of guiding significance to the exploration and recovery of shale oil. However, most studies focus on adsorption and neglect absorption or study it independently, which weakens the understanding of the coupling relationship between adsorption and absorption and the occurrence mechanism of shale oil in kerogen and its associated pores. Based on molecular dynamics (MD) simulation, the kerogen matrix with a smooth surface is constructed, and the general amber force field is adopted to calculate the adsorption and absorption of shale oil in a type II kerogen slit, and the influences of temperature, pressure, and pore diameter on the occurrence of shale oil are also discussed. Molecules absorbed in the kerogen matrix are mainly retained in the free space formed by the accumulation of aliphatic carbon. The effects of temperature on the distribution of shale oil in adsorption and absorption are opposite. High temperature improves the desorption of molecules from the adsorption sites and causes a lower adsorption and greater absorption. In contrast, pressure and pore diameter only slightly influence the distribution of shale oil. Unexpectedly, the result under aqueous conditions shows that the shale oil was absorbed quickly before the formation of water clusters. Once the water clusters are formed due to the strong hydrogen bonding and adsorbed near the N-, S-, and O-containing groups on the kerogen surface, the matrix gaps are blocked due to the size exclusion, and the absorption is suppressed. Additionally, we established the evolution of the ratio of free-adsorbed–absorbed oil at different temperatures and pressures, which provides a new idea and a new method for detecting the occurrence and mobility evaluation of shale oil under reservoir conditions.

A general force field by machine learning on experimental crystal structures. Calculations of intermolecular Gibbs energy with FlexCryst.

Machine learning was employed on the experimental crystal structures of the Cambridge Structural Database (CSD) to derive an intermolecular force field for all available types of atoms (general force field). The obtained pairwise interatomic potentials of the general force field allow for the fast and accurate calculation of intermolecular Gibbs energy. The approach is based on three postulates regarding Gibbs energy: the lattice energy must be below zero, the crystal structure must be a local minimum, and, if available, the experimental and the calculated lattice energy must coincide. The parametrized general force field was then validated regarding these three conditions. First, the experimental lattice energy was compared with the calculated energies. The observed errors were found to be in the order of experimental errors. Second, Gibbs lattice energy was calculated for all structures available in the CSD. Their energy values were found to be below zero in 99.86% of the cases. Finally, 500 random structures were minimized, and the change in density and energy was examined. The mean error in the case of density was below 4.06%, and for energy it was below 5.7%. The obtained general force field calculated Gibbs lattice energies of 259 041 known crystal structures within a few hours. Since Gibbs energy defines the reaction energy, the calculated energy can be used to predict chemical-physical properties of crystals, for instance, the formation of co-crystals, polymorph stability and solubility.

Metaplectic operator approach to Gutzwiller’s trace formula

We derive the Gutzwiller’s trace formula by considering the time-evolution operator of the Hamiltonian which describes an N-dimensional time-dependent generalized harmonic oscillator with general force terms, where the time-evolution operator is composed of metaplectic and Weyl-Heisenberg operators. The Hamiltonian is constructed by expanding a wave packet quadratically in position and momentum operators around a reference trajectory. Using the explicit form of the metaplectic operator recently obtained in (2022, J. Korean Phys. Soc. 80, 95), we give the proof of the well known properties of the metaplectic operator, and using those properties, we derive Gutzwiller’s trace formula and investigate the Maslov index appearing in the formula.

Analysis of Crime, Incarceration, Victimization and Employment of Indigenous Persons in Canada from 2015 to 2021

This study investigated involved a review of trends from five Statistics Canada databases on criminality, victimization, custody in correctional services, adult admissions to community services, and general labour force levels in the 6 years following the release of the December 2015 Truth and Reconciliation Commission Report. Although there did not appear to be a general decline in criminality, victimization, or overall custody of Indigenous persons in Canada from 2015 to 2021, minor improvements in the nature of intra-community victimization, admissions to community services to serve sentences, and increased employment among Indigenous persons in Canada were observed. Discussion focuses on the short- and long-term implications of the TRC report with respect to meaningful impacts on the lives of indigenous people in Canada.

Improving the Force Reconstruction Performance of Vision-Based Tactile Sensors by Optimizing the Elastic Body

The force feedback of vision-based tactile sensors is always expected to be accurate and robust. This work focuses on indicating and lessening the limitation of the structure of the vision-based tactile sensor's elastic body on the distributed force reconstruction performance. The conflict between the accuracy and the robustness of the reconstructed force and the limitation of the elastic body's structure on the accuracy and robustness are discussed based on a general force measurement model of vision-based tactile sensors. Aiming to improve the force reconstruction performance by optimizing the elastic body, we propose a quantitative sensitivity index to evaluate and compare the performance of the elastic body. Under the guidance of the proposed sensitivity index, the methods and principles of optimizing the structure are explored. Finally, the applications of the methods and principles in optimizing the elastic body of two representative vision-based tactile sensors, Tac3D and GelSight, are carried out and significantly improve their force reconstruction performance.

The impurity of praxis: Arendt and Agamben

If politics is understood as a foundational and open-ended activity, a general problem that arises from such a framing concerns the question of how to sustain the possibility of continuous openings without converting action into permanence and closure. In this article, we approach this problematic by treating Hannah Arendt as an exemplary figure in the current of political thought that emphasizes the indeterminate nature of action. We focus more specifically on how Arendt addressed the question of sustaining action by exploring the role of forgiveness, promises, divided power, and principles of action in her thought. While we show that the task of sustaining the indeterminacy of action partly remains an unresolvable paradox for Arendt, a general force underpinning the thought of Giorgio Agamben sheds new light on this paradox. Rather than affirming radical openness and pure praxis as such, Agamben’s work helps accentuate the need of a certain contamination of praxis by its own limit or apparent opposite. Importantly, this allows us to interpret Arendt and the paradoxical task of bestowing some degree of permanence to the open horizon of political action in a decidedly positive light: that praxis implies a moment of impurity is the very force that sustains it without sacrificing its indeterminate nature.

Optimal Design and Dynamic Analysis of a Spring-Actuated Cam-Linkage Mechanism in a Vacuum Circuit Breaker

This study attempted to establish an optimal design and perform dynamic analysis for a spring-actuated cam-linkage composite mechanism in a rated 12 kV, 25 kA vacuum circuit breaker (VCB). The optimal design of the VCB mechanism involves two steps: the first step involves the optimal design of the stiffness of closing springs and the cam profile, based on three-order polynomial motion curve of the follower; the second step involves the optimal design of a four-bar linkage. To minimize the surplus work in the VCB operating mechanism, the overall difference between the general output force and general resistant force of the VCB operating mechanism during the closing operation was adopted as the objective function to be minimized. Furthermore, the differential evolution algorithm with the golden ratio (DE-gr), an efficient and accuracy metaheuristic algorithm, was employed as the optimization method. The dynamic analysis of the optimal operating mechanism was conducted using a MATLAB-coded program and verified by the multibody dynamic software MSC-ADAMS. The dynamic analysis revealed that the optimal design of the VCB mechanism can considerably decrease the average closing velocity of the movable contact and the Hertz stress between the contact surface of the cam and the roller follower.

Identifying Systematic Force Field Errors Using a 3D-RISM Element Counting Correction.

Hydration free energies of small molecules are commonly used as benchmarks for solvation models. However, errors in predicting hydration free energies are partially due to the force fields used and not just the solvation model. To address this, we have used the 3D reference interaction site model (3D-RISM) of molecular solvation and existing benchmark explicit solvent calculations with a simple element count correction (ECC) to identify problems with the non-bond parameters in the general AMBER force field (GAFF). 3D-RISM was used to calculate hydration free energies of all 642 molecules in the FreeSolv database, and a partial molar volume correction (PMVC), ECC, and their combination (PMVECC) were applied to the results. The PMVECC produced a mean unsigned error of 1.01±0.04kcal/mol and root mean squared error of 1.44±0.07kcal/mol, better than the benchmark explicit solvent calculations from FreeSolv, and required less than 15 s of computing time per molecule on a single CPU core. Importantly, parameters for PMVECC showed systematic errors for molecules containing Cl, Br, I, and P. Applying ECC to the explicit solvent hydration free energies found the same systematic errors. The results strongly suggest that some small adjustments to the Lennard-Jones parameters for GAFF will lead to improved hydration free energy calculations for all solvent models.

Interaction of Chondroitin and Hyaluronan Glycosaminoglycans with Surfaces of Carboxylated Carbon Nanotubes Studied Using Molecular Dynamics Simulations

Interaction of β-D-glucopyranuronic acid (GlcA), N-acetyl-β-D-glucosamine (GlcNAc), N-acetyl-β-D-galactosamine (GalNAc) and two natural decameric glycosaminoglycans, hyaluronic acid (HA) and Chondroitin (Ch) with carboxylated carbon nanotubes, were studied using molecular dynamics simulations in a condensed phase. The force field used for carbohydrates was the GLYCAM-06j version, while functionalized carbon nanotubes (fCNT) were described using version two of the general amber force field. We found a series of significant differences in carbohydrate-fCNT adsorption strength depending on the monosaccharide molecule and protonation state of surface carboxyl groups. GlcNAc and GalNAc reveal a strong adsorption on fCNT with deprotonated carboxyl groups, and a slightly weaker adsorption on the fCNT with protonated carboxyl groups. On the contrary, GlcA weakly adsorbs on fCNT. The change in protonation state of surface carboxyl groups leads to the reversal orientation of GlcNAc and GalNAc in reference to the fCNT surface, while GlcA is not sensitive to that factor. Adsorption of decameric oligomers on the surface of fCNT weakens with the increasing number of monosaccharide units. Chondroitin adsorbs weaker than hyaluronic acid and incorporation of four Ch molecules leads to partial detachment of them from the fCNT surface. The glycan-fCNT interactions are strong enough to alter the conformation of carbohydrate backbone; the corresponding conformational changes act toward a more intensive contact of glycan with the fCNT surface. Structural and energetic features of the adsorption process suggest the CH-π interaction-driven mechanism.

Nonlinear taxation and international mobility in general equilibrium

Migration and general equilibrium forces are both known to limit the extent of redistribution due to a migration threat and a trickle-down rationale, respectively. In this paper, we consider these two forces jointly and study the optimal nonlinear taxation of internationally mobile workers in general equilibrium. We show that both forces partly offset each other. In general equilibrium, migration may lower the bottom tax rate but raises the top tax rate, challenging the classical migration-threat argument. Moreover, we demonstrate that migration responses weaken the trickle-down rationale. Both findings can be explained by a novel wage effect on migration and a migration effect on wages, calling for higher top tax rates to amplify pre-tax wage inequality and prevent high-skilled emigration. We calibrate our model to the U.S. economy and illustrate the new effects by comparing the optimal tax schemes with and without migration, as well as with and without endogeneity of wages.

Molecular Dynamics-Assisted Interaction of Vanadium Complex-AMPK: From Force Field Development to Biological Application for Alzheimer's Treatment.

A large part of the world's population is affected by Alzheimer's disease (AD) and diabetes mellitus type 2, which cause both social and economic impacts. These two conditions are associated with one protein, AMPK. Studies have shown that vanadium complexes, such as bis(N',N'-dimethylbiguanidato)-oxovanadium(IV), VO(metf)2·H2O, are potential agents against AD. A crucial step in drug design studies is obtaining information about the structure and interaction of these complexes with the biological targets involved in the process through molecular dynamics (MD) simulations. However, MD simulations depend on the choice of a good force field that could present reliable results. Moreover, general force fields are not efficient for describing the properties of metal complexes, and a VO(metf)2·H2O-specific force field does not yet exist; thus, the proper development of a parameter set is necessary. Furthermore, this investigation is essential and relevant given the importance for both the scientific community and the population that is affected by this neurodegenerative disease. Therefore, the present work aims to develop and validate the AMBER force field parameters for VO(metf)2·H2O since the literature lacks such information on metal complexes and investigate through classical molecular dynamics the interactions made by the complex with the protein. The proposed force field proved to be effective for describing the vanadium complex (VC), supported by different analyses and validations. Moreover, it had a great performance when compared to the general AMBER force field. Beyond that, MD findings provided an in-depth perspective of vanadium complex-protein interactions that should be taken into consideration in future studies.

Does the Job Stress Always Lead to a Negative Stress? Understanding the Effect of Job Stress on Organizational Commitment among General Operations Forces

Does the Job Stress Always Lead to a Negative Stress? Understanding the Effect of Job Stress on Organizational Commitment among General Operations Forces

Calculation of slamming wave loads on monopiles using fully nonlinear kinematics and a pressure impulse model

The design methods for highly nonlinear wave loads on monopile structures has over the past years been extended with methods based on pre-computed fully nonlinear wave kinematics. Yet, the slamming events of the strong sea states cannot currently be predicted with these methods. We here present a simple recipe for the application of a recent pressure impulse based slamming load model in combination with fully nonlinear wave kinematics and validate the results against lab measurements of uni- and multi-directional storm sea states. The experimental slamming loads are extracted from lab measurements equivalent to 954 full scale hours. Six methods for the extraction of the slamming force are developed and analysed in detail, with a final selection of two for the further analysis. The experimental analysis shows that the frequency of slamming is larger in uni-directional sea states relative to sea states with directional spreading, and with slightly smaller force impulses. The calculated slamming frequencies from the measurements are used in the application of the numerical slamming model. It is shown that the application is straightforward and robust and involves an intuitive selection of the model inputs from the incident wave kinematics. A generally good agreement between the model and measurement distributions of the force impulse is observed. The difference between 3D and 2D slamming impulses, though, is found to be larger in the numerical model. This is traced to the numerical particle velocities in the wave crests. The pressure impulse model is next extended by assuming a predefined generic slamming force time variation and through calibration of the peak slamming force, a generally good agreement between the model and ensemble-averaged measured slamming force time series is obtained, given the uncertainty in the slamming load extraction. It is also observed that the commonly used non-dimensional slamming force peak of 2π is unrealistically large in the irregular slamming waves because of the 3D effects of small curling factors.

The influence of force fields on the structure and dynamics of water confined in ZIF-8 from atomistic simulations.

The complexity of modeling flexible crystals, such as ZIF-8, mainly stems from the handling of intramolecular interactions. Numerous force fields have been proposed in the literature to describe the interactions between atoms in ZIF-8. We employ seven force fields to examine the structure and dynamic behavior of water molecules confined in ZIF-8, with the aim of investigating the impact of force fields on simulation results. Various structural characterization methods consistently indicate that the choice of different force fields has quantitative effects but no qualitative effects on the structural characteristics of confined water. Additionally, the force fields do not impact the qualitative description of the diffusion mechanism. Both mean-square displacement and van Hove autocorrelation function reveal two characteristic movements of water molecules diffusing in ZIF-8: a short-time intra-cavity hopping process and a long-time inter-cavity hopping process. However, the framework flexibility is found to play a crucial role in determining the order of spatial arrangement and local structure, self-diffusion coefficient and reorientational dynamics of confined water. Specifically, the DREIDING force field gives rise to an unrealistic stiff framework, enhancing the order of spatial arrangement and diminishing the local ordered structure of confined water. Meanwhile, it results in much slower translational and reorientational dynamics. Hence, the general DREIDING force field cannot be considered for providing a quantitative description of the water structure and dynamics.

Algorithm and Examples of an Agent-Based Evacuation Model

This research establishes a “detect-decide-action” agent-based evacuation model based on the social force model, introducing an active steering force into the basis of the dynamic equation with the combination of the behavioral decision model and the probability model. In the AEM, the detection algorithm is used to identify pedestrians or obstacles within the detection radius to provide the next walking direction and apply the active steering force. The obstacle avoidance algorithm is the core of the “action” link. This research focuses on the establishment of the following and bypassing algorithm when moving in the same direction, and the algorithm of a detour when moving in the opposite direction, applying C++ programming language to achieve the basic evacuation behavior simulation of avoiding pedestrians and obstacles in the actual scene. The results show that compared with the grid model and the general social force model, the agent model (AEM) solves the problem of the distortion of evacuation behavior to some extent, and the pedestrian is more flexible in the choice of evacuation path.

A novel vertical elastic vibration reduction for railway vehicle carbody based on minimum generalized force principle

Aiming at the vertical elastic vibration reduction of a railway vehicle carbody, the traditional technology mainly focuses on the design of modal frequency, the method of increasing damping and the design of dynamic vibration absorber (DVA), with little attention to the design of modal shape. In this paper, a novel vertical elastic vibration reduction method based on the minimum generalized force principle (MGFP) is proposed, i.e., the vertical elastic vibration of carbody is reduced by adjusting its own parameters (weight distribution and stiffness distribution) to control the first-order vertical bending (FVB) modal shape nodes to the carbody–bogie interface positions. Firstly, to better apply MGFP, a factor called generalized force factor (GFF) that can determine the level of generalized force (GF) is proposed. By improving theoretical model of a railway vehicle carbody, the traditional uniform cross-section Euler–Bernoulli beam (UCEB) is replaced by variable cross-section Euler–Bernoulli beam (VCEB) model, and the influencing factors of modal frequency and modal shape node locations can be investigated by the VCEB model. Then, the vertical vehicle system dynamics model is established based on the VCEB carbody model, and the influence of weight distribution, stiffness distribution and carbody–bogie interface positions on the elastic vibration is analyzed under a sweep frequency signal and track irregularities. Finally, the vibration reduction method is verified by a full-scale roller rig test. The theoretical analysis and experimental results show that: by changing the weight distribution or stiffness distribution of the carbody, the FVB modal shape node locations can be effectively controlled, and then combined with the design of carbody–bogie interface positions, the vertical bending elastic vibration of the carbody can be reduced. The vibration reduction method proposed in this paper can be applied to the design of new carbodies or the layout optimization of carbody subsidiary mass.

On Subsonic and Subsonic-Sonic Flows with General Conservatives Force in Exterior Domains

In this paper, we study the irrotational subsonic and subsonic-sonic flows with general conservative forces in the exterior domains. The conservative forces indicate the new Bernoulli law naturally. For the subsonic case, we introduce a modified cut-off system depending on the conservative forces which needs the varied Bers skill, and construct the solution by the new variational formula. Moreover, comparing with previous results, our result extends the pressure-density relation to the general case. Afterwards we obtain the subsonic-sonic limit solution by taking the extract subsonic solutions as the approximate sequences.

High-order direct parametrisation of invariant manifolds for model order reduction of finite element structures: application to generic forcing terms and parametrically excited systems

The direct parametrisation method for invariant manifolds is used for model order reduction of forced-damped mechanical structures subjected to geometric nonlinearities. Nonlinear mappings are introduced, allowing one to pass from the degrees of freedom of the finite-element model to the normal coordinates. Arbitrary orders of expansions are considered for the unknown mappings and the reduced dynamics, which are then solved sequentially through the homological equations for both autonomous and time-dependent terms. It is emphasised that the two problems share a similar structure, which can be used for an efficient implementation of the non-autonomous added terms. Special emphasis is also put on the new resonance conditions arising due to the presence of the external forcing frequencies, which allow predicting phenomena such as parametric excitation and isolas formation. The method is then applied to structures of academic and industrial interest. First, the large amplitude vibrations of a forced-damped cantilever beam are studied. This example highlights that high-order non-autonomous terms are compulsory to correctly estimate the maximum vibration amplitude experienced by the structure. The birth of isolated solutions is also illustrated on this example. The cantilever is then used to show how quadratic coupling creates conditions for the excitation of the parametric instability, and that this feature is correctly embedded in the reduction process. A shallow arch excited with multi-modal forcing is then studied to detail different forcing effects. Finally, the approach is validated on a structure of industrial relevance, i.e. a comb-driven micro-electro-mechanical resonator. The accuracy and computational performance reported suggest that the proposed methodology can accurately predict the nonlinear dynamic response of a large class of nonlinear vibratory systems.