Computer Simulation Study Research Articles

Computational simulation study of the mutation effects on the interaction mechanisms of LSD1 with histone H3 and non-histone Snail1 substrates

Computational simulation study of the mutation effects on the interaction mechanisms of LSD1 with histone H3 and non-histone Snail1 substrates

Computer simulation study of confined oblate hard ellipsoid liquid crystals: Hard-disk–wall interaction

Computer simulation study of confined oblate hard ellipsoid liquid crystals: Hard-disk–wall interaction

Effects of aging-related muscle degeneration on dynamic stability during walking: a musculoskeletal computer simulation study.

Aging-related deficits in the physiological properties of skeletal muscles limit the control of dynamic stability during walking. However, the specific causal relationships between these factors remain unclear. This study evaluated the effects of aging-related deficits in muscle properties on dynamic stability during walking. Walking movements were simulated using two-dimensional musculoskeletal models consisting of 18 Hill-type muscles. To assess the effects of aging-related deficits in muscle function on dynamic stability during walking, five models with different muscle properties were created, namely young adult (YA) and older adult (OA) models, models with reduced maximum isometric muscle force, reduced maximum muscle contraction velocity, and prolonged muscle deactivation time (∆F, ∆V, and ∆T models, respectively). The margin of stability (MoS) was used as a measure of dynamic stability during walking. The MoS value of the OA model was greater than that of the YA model, and the ∆F model yielded a larger MoS value than those of the ∆V and ∆T models. Therefore, the OA model achieved a more dynamically stable state than the YA model and the ∆F model required a more stable state to sustain continuous walking compared to the ∆V and ∆T models. These findings indicate that aging-related deficits in muscle function limit the control of dynamic stability during walking with the degeneration of maximum isometric muscle force being the most influential factor. These findings could aid in the development of an intervention program to reduce the risk of falls in older adults effectively.

Performance improvement of manipulator actuated by pneumatic artificial muscles based on synergetic control and social spider optimisation algorithm

The manipulator actuated by pneumatic artificial muscles (PAM) is a widely used type of robotic arm in industrial automation. However, its performance can be limited by non-linear dynamics and uncertainties in the system. To overcome these limitations, this paper proposes a synergetic control strategy (SACT) to improve the performance of the SACT, a social spider optimisation algorithm (SSO) has been suggested for adjusting its parameters. To verify the performance of a PAM-actuated manipulator based on an optimal SACT controller, a computer simulation study was conducted using MATLAB software. Moreover, a comparison study between the optimal synergetic algorithm control theory and the optimal sliding mode controller (SMC) has been made in terms of robustness and transient behaviour characteristics. The provided simulation results have shown that the SACT controller exhibited quicker convergence towards the desired trajectory and maintained a lower steadystate error as compared to the SMC controller. Additionally, the SACT controller demonstrated more resilience to variations in parameters and showed more robust characteristics.

A comparative study of simulated electric fields of transcranial magnetic stimulation targeting different cortical motor regions.

This computational simulation study investigates the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EF) in primary motor cortex (M1) and secondary motor areas. Our results reveal high interindividual variability in the strength of TMS-induced EF responses in secondary motor areas, relative to the stimulation threshold in M1. Notably, the activation of the supplementary motor area requires high-intensity stimulation, which could be attributed to the greater scalp-to-cortex distance observed over this area. These findings emphasize the importance of individualized planning using computational simulation for optimizing neuromodulation strategies targeting the cortical motor system.

Short-time collective dynamics of an ionic liquid: A computer simulation study with non-polarizable and polarizable models, and abinitio molecular dynamics.

Molecular dynamics (MD) simulation is used to study the intermolecular dynamics in the THz frequency range of the ionic liquid 1-ethyl-3-methylimidazolium bis(fluorosulfonyl)imide, [C2C1im][FSI]. Non-polarizable and polarizable models for classical MD simulation are compared using as quality criteria abinitio molecular dynamics (AIMD) and experimental data from far-infrared (FIR) spectroscopy and previously published data of inelastic x-ray scattering (IXS). According to data from IXS spectroscopy, incorporating polarization in the classical MD simulation has relatively little effect on the dispersion curve (excitation frequency vs wavevector) for longitudinal acoustic modes. When the AIMD simulation is used as a reference, the polarizable model leads the time correlation functions of velocity, mass, and charge currents to relax abnormally quickly. The charge current spectra from the AIMD simulation and the non-polarizable model agree with the experimental FIR spectrum, while the polarizable model gives an excessively broad band. When compared to the non-polarizable model, the polarizable model does improve the calculation of transport coefficients (diffusion coefficient, viscosity, and conductivity); however, it yields overdamped short-time collective dynamics.

Computational Simulation Study-Based Formulation Development and Characterization of MethylprednisoloneLoaded Nanoparticles Containing Chitosan and Pectin to Treat Nocturnal Asthma.

Nocturnal asthma (NA) is a high-prevalence disease that causes severe respiratory issues, leading to death from early midnight to early morning. In this research, nanoparticulate drug delivery system of methylprednisolone (MP) was developed using chitosan (CH) and pectin (PEC). MP is a synthetic corticosteroid medication widely used for its potent anti-inflammatory activity. Computational simulation study (AI-based blend analysis algorithm) was used to identify a better-mixing polymer with MP. MP nanoparticles were formulated by the ionic gelation method with the combination of CH and PEC. To modify the drug release properties, the formed beads were coated with chitosan succinate (CSSC). The morphological characteristics of the beads were determined by SEM analysis. The X-ray radiographic imaging study was used to observe the intactness of MP beads. Histopathological studies were also carried out to find out the toxicity of the beads in the organs of rats. Pectin and chitosan polymers were selected based on the computational simulation study. SEM analysis revealed that the beads had a spherical shape with a rough outer surface. CSSC-coated beads achieved sustained drug release for up to 24 h. X-ray imaging demonstrated the stability of the beads in acidic pH conditions. In vivo pharmacokinetic studies showed that CSSC-coated beads were more stable in the gastrointestinal tract (GIT) than PEC-CH beads and the pure drug. Histological evaluation confirmed that the beads are nontoxic and safe for use in rats. Based on the findings, it was concluded that CSSC-coated beads of MP exhibited superior release properties, making them suitable for a chronomodulated drug delivery system.

A Computer Simulation Study on Ion Optics Aiming at the Realization of Projection-Type Mass Spectrometry Imaging

The projection mode in mass spectrometry imaging (MSI) obtains ion images by retaining the spatial distribution of desorbed ions immediately after their generation as the ion images, then projecting them onto an ion detector of time-of-flight mass spectrometry. Compared to conventional MSI, projection-type MSI can deliver overwhelmingly higher spatial resolution. The mass resolution of projection-type MSI can be improved by a technique named post extraction differential acceleration (PEDA). To assess the feasibility of projection-type MSI with minimal modification of a commercially available laser desorption/ionization time-of-flight mass spectrometer, ion trajectory simulations were performed using the ion optics simulation program SIMION. Under boundary conditions that reproduce the ion acceleration region of the commercial mass spectrometer with a high fidelity, the trajectory simulation results were obtained for a huge number of combinations of ion masses, initial conditions, PEDA parameters, etc. The data analysis provided useful findings that can lead to the realization of projection-type MSI based on the modified commercial mass spectrometer, for instance, the imaging conditions for ion images in the commercial equipment, guidelines for optimizing PEDA parameters, and the effects of differences in PEDA high-voltage rising waveforms.

Biomechanical Evaluation of Physical Examination Tests for Rotator Cuff Tears - A Computer Simulation Study.

Numerous physical diagnostic shoulder tests have been established to determine the presence of rotator cuff tears and to identify the affected muscles. However, reported sensitivities and specificities of these tests vary strongly. The aim of this study was to identify diagnostic postures that are biomechanically most sensitive in identifying rotator cuff lesions and compensation mechanisms. A musculoskeletal modelling study investigating muscle activity in healthy shoulders as well as in shoulders with anterior, superior, and posterosuperior rotator cuff tear patterns, was conducted. Muscle moment arms and muscle synergism for the Lift-off and Bear Hug tests, Jobe and Full-can tests and Infraspinatus and Hornblower tests were compared for healthy and pathological models. In a healthy model the Lift-off test showed significantly higher subscapularis activity compared to the Bear Hug test (p<0.001). Teres minor and infraspinatus activity were threefold and twofold higher, in the Hornblower than the Infraspinatus test, respectively. In superior tests, supraspinatus activity was more than twofold lower than lateral deltoid activity and synergistic activity increase was smallest (Δ 1-3% in deltoid). Activity increase was highest in posterosuperior tests for the teres minor with 66.4% activity increase in the Infraspinatus test (p<0.001) and 81.3% increase in the Hornblower test (p<0.001). The Lift-off test was significantly more sensitive in detecting subscapularis tears and the Hornblower test was more effective in assessing teres minor integrity in posterosuperior tears. Both, Jobe and Full-can tests demonstrated low biomechanical sensitivity in the detection of superior rotator cuff tears.

Choosing a standard CPC by analyzing thermal performance in regions with climatic and geographical disparities

This is a computational simulation study that employs an analytical method implemented in MATLAB® to investigate various configuretions of Compound Parabolic Concentrator (CPC) with fully illuminated inverted V absorber and determine a universal solar device, optimized, applicable and used for process heat, enabling service in regions with significant latitude differences, without substantial performance losses regardless of specific local geometric parameters. The input data consist only of the Average Daily Global Solar Radiation, choosing two Brazilian cities with distinct irradiation characteristics: Caruaru, PE and Porto Alegre, RS. A comparative study and optimization analysis in relation to the acceptance angle (qa) was conducted with different CPC configuretions, to determine which of these (65°; 56.40°; 50°; 45.60°; 38.70°; 33.75°, 30°) would present the best performance and carry out an exchange study. Concluding that the difference of energy generation, under these conditions, not discrepant, allowing for the use of a single type of CPC (qa=56.40° and a truncation angle qt =45.60°), generated the highest annual energy of 34,918.28 Wh/m² and had the lower Sum Generated Energy Ratios (Energy Caruaru/Energy Porto Alegre) equal to 9.86, without any structure modifications to serve both regions - this is the standard CPC.

Individual differences in escalation of commitment: a multi-level adaptive learning perspective

Previous studies have found stable individual differences in decision-making under escalation situations. Conventionally, the differences have been attributed to dispositional factors. In this paper, we offer multi-level adaptive learning as an alternative, positing that stable individual differences can develop (a) from an equal starting point at which there are no individual differences among all simulated learners, and (b) without the presumption of influences from dispositional factors. The results of three computer simulation studies showed that after sufficient learning trials, simulated individuals developed the key characteristics of stable individual differences in escalation of commitment: (a) a stable escalation tendency, (b) stable individual differences in escalation tendency, (c) decreases in stability of individual differences as more learning occurs, and (d) decreases in test–retest correlation as the test–retest interval increases. The findings suggest that adaptive learning can explain the emergence and development of individual differences in escalation of commitment without the assumption of dispositional factors.

The nature of the hydrophobic interaction varies as the solute size increases from methane's to C60's.

The hydrophobic interaction, often combined with the hydrophilic or ionic interactions, makes the behavior of aqueous solutions very rich and plays an important role in biological systems. Theoretical and computer simulation studies have shown that the water-mediated force depends strongly on the size and other chemical properties of the solute, but how it changes with these factors remains unclear. We report here a computer simulation study that illustrates how the hydrophobic pair interaction and the entropic and enthalpic terms change with the solute size when the solute-solvent weak attractive interaction is unchanged with the solute size. The nature of the hydrophobic interaction changes qualitatively as the solute size increases from that of methane to that of fullerene. The potential of mean force between small solutes has several well-defined extrema, including the third minimum, whereas the potential of mean force between large solutes has the deep contact minimum and the large free-energy barrier between the contact and the water-bilayer separated configurations. The difference in the potential of mean force is related to the differences in the water density, energy, and hydrogen bond number distributions in the vicinity of the pairs of hydrophobic solutes.

Regulating Steric Hindrance in Redox Coupling of Single Organic Molecule for High Performance Organic Batteries

Since the use of tricarbonyl compounds (e.g. dichloroisocyanuric acid) as electrode materials for primary lithium batteries dates back to the 1960s, organic molecules have received significant attention as a means to further advance the state-of-the-art electrode materials for rechargeable batteries due to their advantages, including abundance, high energy density, design flexibility, environmentally benign nature, mild synthesis processes, and cost competitiveness. Numerous molecular design strategies have been employed to achieve high performance in organic electrode materials for rechargeable batteries. For examples, the organic molecular structure can be optimized to provide high specific capacity by minimizing the redox-inactive parts, exploiting multiactive centers, or introducing electron activating and deactivating groups. In addition, cycle stability can be controlled by polymerization of the active-molecules and electrical conductivity can be increased by enhancing electron delocalization, inter- (p-d) and intra-molecular (p-p) conjugation in aromatic rings of the organic molecules.Herein, we provide a novel design of organic electrode for high discharge voltage with superior cycling stability in rechargeable battery by using steric effect of substituted the single molecule. 16,17-dihydroxyviolanthrone (DHV) molecule was used as a single molecule model for control group because the violanthrone compound has a planar conformation overlapping sp2 hybridized carbon and its hydroxyl groups that can be substituted with a variety of substituents. The electrochemical performance of DHV cathode and its reversible redox process in rechargeable battery system were demonstrated through experimental and theoretical identification at the first time. To further advance the battery performance of the DHV through the steric hindrance effect, we substituted main functional group (-OH) of DHV nearby p-type redox center with long-chain alkoxy group (-OC8H17 or -OC10H21) leading to ether, which are dioctiloxyviolanthrone (DOV) and didecyloxyviolanthrone (DDV), respectively.In comparison to DHV, DOV and DDV showed significant increase of redox potential of the oxidation reaction allowing battery with around 0.6 V higher operating voltage. We further substantiated the steric hindrance effect from long-chain alkoxy groups on coupling electrolyte anion (PF6 -) with charged DOV and DDV via computational simulation and theoretical studies based on density functional theory (DFT). Moreover, we showed that the bipolar nature of the violanthrones allows its application in symmetrical cells, though the cycling performance was limited by the reduction reaction stability. Additionally, we demonstrated that finding of the more suitable electrolyte could lead to greatly enhanced stability of the violanthrone electrodes allowing up to 2000 cycles without capacity reduction and reduced voltage decay. Finally, based on various analytical methods, we demonstrated that the oxidation occurs through withdrawing of the delocalized electrons from the large conjugated structure of the violanthrones, and that the main the p-type redox site could be determined to be the moiety of (-(ROC)C-C-C-C(COR)-). Thus, this molecular design approach allows development of organic cathode with a high redox potential, comparable to the conventional cathode materials, and potentially may lead to future all-organic symmetric batteries.

A structure-based approach to discover a potential isomerase Pin1 inhibitor for cancer therapy using computational simulation and biological studies

Peptidyl-prolyl cis/trans isomerase Pin1 occupies a prominent role in preventing the development of certain malignant tumors. Pin1 is considered a target for the treatment of related malignant tumors, so the identification of novel Pin1 inhibitors is particularly urgent. In this study, we preliminarily predicted eight candidates from FDA-approved drug database as the potential Pin1 inhibitors through virtual screening combined with empirical screening. Therefore, we selected these eight candidates and tested their binding affinity and inhibitory activity against Pin1 using fluorescence titration and PPIase activity assays, respectively. Subsequently, we found that four FDA-approved drugs showed good binding affinities and inhibition effects. In addition, we also observed that bexarotene can reduce cell viability in a dose-dependent and time-dependent manner and induce apoptosis. Finally, we inferred that residues K63, R68 and R69 are important in the binding process between bexarotene and Pin1. All in all, repurposing of FDA-approved drugs to inhibit Pin1 may provide a promising insight into the identification and development of new treatments for certain malignant tumors.

Computational Simulation and Biophysical Study on Cerium Chloride-Induced B-to-Z Transition in (CG) n DNA.

Rare earth elements have been shown to trigger the B-to-Z DNA transition in diverse self-assembled branched DNA architectures. Herein, we investigated the influence of cerium chloride on the conformational changes of DNA sequences containing repeated cytosine-guanine (CG)6-12 or guanine-cytosine (GC)6-12 sequences. The CD results show that (CG)6-12 repeats were susceptible to the formation of Z-DNA at low concentrations of CeCl3. On the other hand, (GC)6-12 is unable to undergo B-Z DNA transition and instead exhibits condensation with a similar amount of CeCl3. The CD signature was found to be different and unique in both alternate repeats during the interaction with CeCl3. The sequence-specific effects on the B-Z transition are based on the order of nucleotides in DNA. With the addition of EDTA, the Z-form of DNA is reverted to the native B-form. Further, we have reported the positive zeta potential of CeCl3-induced Z-DNA in contrast to the negative zeta potential of B-DNA. The differential zeta-potential value during the B-Z transition is complementary to the conformational changes of DNA. The molecular simulation study also supports the sequence-specific conformational change between the B- and Z-forms of DNA molecules. This newly described reversible topological and sequence-dependent transition is crucial for understanding the structural and biological roles of Z-DNA in response to CeCl3.

Decreased Knee Extensor Torque During Single-Limb Stance: A Computer Simulation Study of Compensations and Consequences

Background/Objectives: For over 50 years, it has been suggested that the plantar flexors and hip extensors can compensate for weak knee extensors and prevent collapse of the leg during a single-limb stance. However, the effects of these compensations have not been studied thoroughly. The purpose of this computer simulation study was to determine, for a given posture, the hip and ankle net joint torque (NJT) required to prevent leg collapse due to systematic decreases in knee NJT and to determine the effect of these compensations on the horizontal ground reaction force. Methods: Single-limb stance was simulated using a static, multisegmented model in eight different postures. For each posture, the knee NJT was systematically decreased. The ankle and knee NJT necessary to prevent lower extremity collapse, along with any net horizontal ground reaction forces, were then calculated. Results: Decreases in knee NJT required linear increases in ankle and hip NJT to prevent the limb from collapsing. There were greater increases in ankle NJT compared to hip NJT, resulting in posteriorly-directed horizontal ground reaction forces. While the magnitudes were different, these findings applied to all postures simulated. Conclusions: For a given posture, ankle and hip NJTs can compensate for a decrease in knee NJT. However, this resulted in a horizontal ground reaction force, which was in the posterior direction for all the postures examined. This horizontal ground reaction force would induce an acceleration on the body’s center of mass that, if not accounted for, could have deleterious effects on achieving a task objective.

The influence of glycine on β-lactoglobulin amyloid fibril formation – computer simulation study

Abstract Amyloids are protein aggregates involved in various protein condensation diseases. Our study aims to investigate the influence of glycine on the fibrillization mechanism of β-lactoglobulin (BLG), a model protein known to form amyloid fibrils from hydrolysed peptides in low pH aqueous solutions. We conducted atomistic molecular dynamics simulations of aqueous solutions of native and unfolded BLG in glycine buffer at pH 2.0. During the simulations we put our focus on analysing protein-protein/buffer interactions, structural electrostatic potential mapping, and the residence times of glycine and glycinium near specific amino acid residues. Glycinium cations were found to preferentially interact with specific protein residues potentially masking the outer disulfide bonds, affecting thiol deprotonation and influencing disulfide scrambling equilibrium. These interactions can potentially hinder hydrolysis and change the fibrillization pathway. Further investigations, such as constant pH MD simulations, simulations on disulfide bounded oligomers are warranted to validate these findings and deepen our understanding of protein aggregation mechanisms.

Elucidation of the Binding Interaction between β-sitosterol and Lysozyme using Molecular Docking, Molecular Dynamics and Surface Plasmon Resonance Analysis.

In this study, the binding behavior of β-sitosterol with lysozyme (LZM) was elucidated by surface plasmon resonance (SPR), computational molecular docking and molecular dynamics simulation studies. Chicken egg white lysozyme (CEWLZM) served as a model protein. Tri-N-acetylchitotriose (NAG3) was used in the redocking experiments to generate precise binding location of the protein. β-sitosterol displayed a slightly better binding energy (-6.68±0.04 kcal/mol) compared to NAG3. Further molecular dynamics simulations and MMPBSA analysis revealed that residues Glu35, Gln57-Asn59, Trp62, Ile98, Ala107 and Trp108 contribute to the binding energy. Then, 2.5 mg/mL CEWLZM, 1X PBS buffer (pH 7.4) as running and coupling buffers, 30 μL/min as flow rate were applied for SPR analysis. Serial β-sitosterol injections (20-150 μM) were performed through SPR sensor surface. According to SPR binding study, KD value for β-sitosterol-CEWLZM binding interaction was calculated as 71.34±9.79 μM. The results could provide essential knowledge for nutrition, pharmaceutical science, and oral biology.

A computer simulation study of a chiral active ring polymer.

We investigate a ring polymer under the influence of chiral active Brownian forces in two dimensions using coarse-grained computer simulations. We observe a non-monotonic behavior of the radius of gyration of an active Brownian ring as a function of active force. However, the shrinkage of the ring in the intermediate strength of active forces becomes more pronounced in the presence of chiral active forces, and the shrinkage is monotonic at a given activity level as a function of the angular frequency controlling the direction of the active force. The distribution of radius of gyration, inter-monomer distance, and radial distribution suggest that the monomers come close to each other, eventually leading to the shrinkage of the ring. Moreover, the bond-correlation suggests that the chirality introduces a local folding of the monomers. Furthermore, using the diameter correlation function, we show that the ring performs tank-treading motion with a frequency following power-law relation with active force with exponent 3/2. The mean squared displacement of the monomers further assists the tank-treading dynamics by exhibiting oscillatory behavior.

Effect of natural ventilation on aerosol transmission and infection risk in a minibus

High passenger density, prolonged exposure, and close interpersonal distance create a high infection risk (IR) in minibuses. While improving natural ventilation induced by turbulent airflows is essential for controlling IR in minibuses, comprehensive studies on its effectiveness are lacking. To address this, we conducted computational fluid dynamics simulations studies coupling indoor–outdoor turbulent airflows to examine the impact of window opening locations, window opening sizes, and initial droplet diameters (dp) on the ventilation airflow and dispersion of pathogen-laden droplets. Results show that the surrounding turbulent flow patterns create higher surface pressure at bus rear than bus front, which is a key factor influencing bus ventilation. When all windows are closed, ventilation is primarily provided by skylights at bus rooftops. Ventilation through only two skylights resulted in an air change rate per hour (ACH) of 17.55 h−1, leading to high IR of passengers. In contrast, fully opening front and rear windows increases ACH by 27.28-fold to 478.79 h−1, significantly reducing IR by 1–2 orders of magnitude compared to skylight ventilation. Expanding window opening sizes can effectively enhance ventilation when both front and rear windows open (attributed to the pumping effect), while is ineffective when only front windows open. To reduce IR in minibuses, we recommend opening multiple windows at the bus front and rear. Even if the total opening area of the front and rear windows is only two-thirds of that of the front window, its ACH is 2.8 times more than only opening front windows.