Docking Mechanism Research Articles

Biocompatibility of Veratric Acid-Encapsulated Chitosan/Methylcellulose Hydrogel: Biological Characterization, Osteogenic Efficiency with In Silico Molecular Modeling.

The limitations of graft material, and surgical sites for autografts in bone defects treatment have become a significant challenge in bone tissue engineering. Phytocompounds markedly affect bone metabolism by activating the osteogenic signaling pathways. The present study investigated the biocompatibility of the bio-composite thermo-responsive hydrogels consisting of chitosan (CS), and methylcellulose (MC) encapsulated with veratric acid (VA) as a restorative agent for bone defect treatment. The spectroscopy analyses confirmed the formation of CS/MC hydrogels and VA encapsulated CS/MC hydrogels (CS/MC-VA). Molecular analysis of the CS-specific MC decamer unit with VA complex exhibited a stable integration in the system. Further, Runx2 (runt-related transcription factor 2) was found in the docking mechanism with VA, indicating a high binding affinity towards the functional site of the Runx2 protein. The formulated CS/MC-VA hydrogels exhibited biocompatibility with the mouse mesenchymal stem cells, while VA promoted osteogenic differentiation in the stem cells, which was verified by calcium phosphate deposition through the von Kossa staining. The study results suggest that CS/MC-VA could be a potential therapeutic alternative source for bone regeneration.

A static balancing mechanism with continuously variable payload capacity for space docking simulation

In this paper, a novel static balancing mechanism is presented to realize gravity compensation in the application of the space docking simulation. By optimizing the relative positions of the compensation pulley block and suspension pulley block, the proposed gravity balancing device achieves static balance in geometry and hence is applicable to continuous variable payload environments. The static balancing mechanism is developed firstly, and its design philosophy is described in detail. By adopting the genetic algorithm (GA) and steepest descent method (SDM) simultaneously, the optimal structural configuration with small trajectory fluctuation in the direction of gravity is obtained. Furthermore, the effect of structural parameters on gravity compensation performance is evaluated. Experimental results and error analysis demonstrate the gravity balancing capability, which indicates the rationality and effectiveness of the proposed device in the space docking condition.

Deciphering the interaction mechanism of natural actives against larval proteins of Aedes aegypti to identify potential larvicides: a computational biology analysis

Aedes aegypti is the target for repellents to curb incidences of vector-borne diseases. Stopping breeding of this mosquito species at its larval stages helps in controlling spread of insect-borne diseases. Therefore, the present study focused on deciphering the mechanism of interaction of selected natural actives against larval proteins of A. aegypti to identify potential natural alternative larvicides. 65 larval proteins were identified from literature, whose structures were modelled and validated using RaptorX and ProCheck. 11 natural actives were selected for predicting their ligand properties and toxicities via Toxicity Estimation Software Tool and ProTox-II. Molecular docking studies were carried out using POAP followed by 100 ns molecular dynamic simulation studies for top three best docked complexes to better understand the robustness of docking, complex stabilities and molecular mechanisms of interactions. Toxicity predictions revealed that 6 molecules belonged to toxicity class 4, and five to toxicity class 5, implying that they were all safe to use. Complexes goniothalamin-translation elongation factor (−10 kcal/mol), andrographolide-acetyl-CoA C-myristoyltransferase (−9.2 kcal/mol) and capillin-translation elongation factor (−8.4 kcal/mol) showed best binding energies. When simulated, capillin-translation elongation factor showed most stability, while the remaining two also evidenced robust docking. Evolutionary studies for top two larval proteins disclosed 100 other insect species in which these proteins can be targeted using various larvicides. Protein-protein interaction network analysis revealed several protein pathways that might be affected due to aforesaid naturals. Therefore, this study provides computational insights into the molecular interaction of naturals against larval proteins, acting as potential natural larvicides. Communicated by Ramaswamy H. Sarma

New natural compound inhibitors of PDGFRA (platelet-derived growth factor receptor α) based on computational study for high-grade glioma therapy.

High-grade glioma (HGG) is a malignant brain tumor that is common and aggressive in children and adults. In the current medical paradigm, surgery and radiotherapy are the standard treatments for HGG patients. Despite this, the overall prognosis is still very bleak. Studies have shown that platelet-derived growth factor receptor α (PDGFRA) is an essential target to treat tumors and inhibiting the activity of PDGFRA can improve the prognosis of HGG. Thus, PDGFRA inhibitors are critical to developing drugs and cancer treatment. The purpose of this study was to screen lead compounds and candidate drugs with potential inhibitors against platelet-derived growth factor receptor α (PDGFRA) from the drug library (ZINC database) in order to improve the prognosis of patients with high-grade glioma (HGG). In our study, we selected Imatinib as the reference drug. A series of computer-aided technologies, such as Discovery Studio 2019 and Schrodinger, were used to screen and assess potential inhibitors of PDGFRA. The first step was to calculate the LibDock scores and then analyze the pharmacological and toxicological properties. Following this, we docked the small molecules selected in the previous steps with PDGFRA to study their docking mechanism and affinity. In addition, molecular dynamics simulation was used to determine whether the ligand-PDGFRA complex was stable in nature. Two novel natural compounds 1 and 2 (ZINC000008829785 and ZINC000013377891) from the ZINC database were found binding to PDGFRA with more favorable interaction energy. Also, they were predicted with less Ames mutagenicity, rodent carcinogenicity, non-developmental toxic potential, and tolerant with cytochrome P450 2D6 (CYP2D6). The dynamic simulation analysis demonstrated that ZINC000008829785-PDGFRA and ZINC000013377891-PDGFRA dimer complex had more favorable potential energy compared with Imatinib, and they can exist in natural environments stably. ZINC000008829785 and ZINC000013377891 might provide a solid foundation for drugs that inhibit PDGFRA in HGG. In addition to being safe drug candidates, these compounds had important implications for improving drugs targeting PDGFRA.

A study on a spacecraft docking system which completes enclosure immediatelly after initial contact

A study on a spacecraft docking system which completes enclosure immediatelly after initial contact

Vision Based Docking of Multiple Satellites with an Uncooperative Target

With the ever-growing number of space debris in orbit, the need to prevent further space pollution is becoming more and more apparent. Refueling, servicing, inspection and deorbiting of spacecraft are some example missions that require precise navigation and docking in space. Having multiple, collaborating robots handling these tasks can greatly increase the efficiency of the mission in terms of time and cost. This article will introduce a modern and efficient control architecture for satellites on collaborative docking missions. The proposed architecture uses a centralized scheme that combines state-of-the-art, ad-hoc implementations of algorithms and techniques to maximize robustness and flexibility. It is based on a Model Predictive Controller (MPC) for which, an efficient cost function and constraint sets are designed to ensure safe and accurate docking. A simulation environment is also presented to validate and test the proposed control scheme.

Mechanisms of Docking of Superoxide Ions in the Catalytic Cycle of Manganese and Iron Superoxide Dismutases

n this paper, we propose an approach to resolving some questions about the catalytic action of manganese and iron superoxide dismutases. At the level of a pure quantum-chemical calculation using an ORCA 5.0.3 program, a PBE functional and a def2-SVP and def2-TZVP basis sets, the possible mechanisms of superoxide ions binding to the active sites of enzymes, the electron transfer distances and their characteristics were established. It is shown that the initial form of the fifth ligand in both active sites is the hydroxide ion OH–. Before the primary electron transfer, active sites are protonated, the hydroxide ion is converted into a water molecule H2O. Primary electron transfers from the superoxide ion to Mn3+-SOD and Fe3+-SOD occur by the associative mechanism, with the formation of an octahedral complex, at a transfer distance of 1.95 Å and 2.56 Å, respectively. At the second stage, the superoxide ion accepts the electron by the substitution mechanism from Mn2+- SOD at the transfer distance of 2 Å to form bonds with the water molecule and a tyrosine. The superoxide ion accepts the electron from Fe2+-SOD through the outer-sphere mechanism, where it binds to a histidine and the water molecule at the transfer distance of 4.24 Å.

Safety-Critical Control for Systems With Impulsive Actuators and Dwell Time Constraints

This paper presents extensions of control barrier function (CBF) and control Lyapunov function (CLF) theory to systems wherein all actuators cause impulsive changes to the state trajectory, and can only be used again after a minimum dwell time has elapsed. These rules define a hybrid system, wherein the controller must at each control cycle choose whether to remain on the current state flow or to jump to a new trajectory. We first derive a sufficient condition to render a specified set forward invariant using extensions of CBF theory. We then derive related conditions to ensure asymptotic stability in such systems, and apply both conditions online in an optimization-based control law with aperiodic impulses. We simulate both results on a spacecraft docking problem with multiple obstacles.

Computational Modeling on Binding Interactions of Cyclodextrin s with the Human Multidrug Resistance P-glycoprotein Toward Efficient Drug-delivery System Applications.

Herein, molecular docking approaches and DFT ab initio simulations were combined for the first time, to study the key interactions of cyclodextrins (CDs: α-CD, β-CD, and γ-CD) family with potential pharmacological relevance and the multidrug resistance P-gp protein toward efficient drug-delivery applications. The treatment of neurological disorders and cancer therapy where the multiple drug-resistance phenomenon mediated by the P-gp protein constitutes the fundamental cause of unsuccessful therapies. To understand more about the CD docking mechanism and the P-gp. In order to achieve the main goal, the computational docking process was used. The observed docking-mechanism of the CDs on the P-gp was fundamentally based on hybrid backbone/side-chain hydrophobic interactions,and also hybrid electrostatic/side-chain interactions of the CD-ligands' OHmotifs with acceptor and donor characteristics, which might theoretically cause local perturbations in the TMD/P-gp inter-residues network, influencing ligand extrusion through the blood-brain barrier. P-gp residues were conformationally favored. Despite the structural differences, all the cyclodextrins exhibit very close Gibbs free binding energy values (or affinity) by the P-gp binding site (transmembrane domains - TMDs). The obtained theoretical docking-mechanism of the CDs on the P-gp was fundamentally based on hybrid backbone/side-chain hydrophobic interactions, and also hybrid electrostatic/side-chain interactions of the OH-motifs of the CD-ligands with acceptor and donor properties which theoretically could induce allosteric local-perturbations in the TMDs-inter-residues network of P-gp modulating to the CD-ligand extrusion from the blood-brain-barrier (or cancer cells). Finally, these theoretical results open new horizons for evaluating new nanotherapeutic drugs with potential pharmacological relevance for efficient drug-delivery applications and precision nanomedicine.

Magnetic-frozen plasma loop far-distance deliver and electromagnetic capture of companion spacecraft

Spacecraft relative motion actuated by inter-craft electromagnetic force/torque provides an attractive way without propellant consumption and plume contamination, and has high-precision control capability of continuous, reversible, synchronous and non-contacting. However, magnetic actuation is limited with distance, yielding a small operating region. Magnetic actuation far-distance delivery based on plasma loop is a revolutionary approach which freezes strong magnetic field in the plasma loop and shoots it with ultra-high speed, and could be exploited to greatly expand the operating region of magnetic actuation. In this paper, the basic principle, capability, and application with companion spacecraft electromagnetic capture are analyzed.

침대 연동 이동식 재활 운동기 개발을 위한 침대-운동기 도킹 메커니즘

본 논문에서는 침대와 연동되는 재활 운동기 시스템에 적용하기 위한 침대-운동기 도킹 메커니즘을 제안 할 것이다. 연구의 최종 목표는 요양원 및 요양병원에서 침대 위주의 생활을 하는 고령자 및 환자를 위한 이동식 운동기 시스템을 개발 하는 것이다. 이를 위한 이동식 운동기 시스템은 운동 시 발생하는 하중 및 환자의 체중 등의 부하에 대해 안정적인 자세를 유지할 수 있어야 한다. 운동기를 침대에 안정적으로 고정시킬 수 있으면 운동기를 소형, 경량의 이동식으로 제작 할 수 있다. 이를 위해 본 논문에서는 운동기와 침대를 기계적으로 결합하는 도킹 메커니즘을 제안한다. 제안하는 도킹 메커니즘은 간단한 페달의 조작으로 운동기를 침대에 큰 힘으로 정확한 위치에 고정할 수 있다. 제안하는 도킹 메커니즘의 특징 및 장점을 설명하기 위해 기구학적 해석 및 간단히 제작된 실험 모델을 활용한 실험 결과를 제시할 것이다.

Attitude Error and Contact Influencing Characteristic Analysis for a Composite Docking Test Platform

The design and analysis of a new type of three-jaw docking mechanism capable of space rendezvous and docking are presented. In addition, a composite docking test platform capable of both vertical and horizontal docking is created. On the basis of kinematics theory, a global coordinate system is built, and the attitude error is assessed based on the error angle. On the basis of dynamic theory, the multi-body dynamic differential equation of the composite docking platform is derived, and the impact-induced interaction state of the locking pawls is studied. The simulation software is then used to jointly simulate the test platform and the docking mechanism under the two conditions of frontal and oblique docking, and to analyze the attitude law caused by the change of docking impact force. This provides a solid foundation for future research into the application of space rendezvous theory to small spacecraft.

An adaptive and dynamic lens-flare-free single-pixel imaging method for spacecraft docking

Lens flare, the photographic artifact produced by reflecting and scattering a powerful incident light within a camera lens group, can severely degrade image quality and mislead the image-based processing task. Existing solutions typically depend on sophisticated optics design or complex image postprocessing algorithms to reduce lens flare. This paper demonstrates a direct reconstruction of the target feature by single-pixel imaging with a simple optics design and no image postprocessing. A novel sampling strategy is proposed for spacecraft docking, which utilizes Fourier single-pixel imaging methods to capture a specific feature at an ultralow sampling ratio. Simulation and experiments demonstrate that the proposed method can image the feature with a sampling ratio of 4.8% at a video frame rate while almost eliminating the impact of the ring effect. This paper provides a new perspective for achieving lens-flare-free, video-framerate and low-data-throughput imaging in space tasks, which has potential in many imaging-based applications.

A Novel RANKL-Targeted Furoquinoline Alkaloid Ameliorates Bone Loss in Ovariectomized Osteoporosis through Inhibiting the NF-κB Signal Pathway and Reducing Reactive Oxygen Species.

Dysregulation of osteoclast-osteoblast balance, resulting in abnormal bone remodeling, is responsible for postmenopausal osteoporosis (PMOP) or other secondary forms of osteoporosis. We demonstrated that dictamnine (DIC), a novel RANKL-targeted furoquinoline alkaloid, inhibits osteoclastogenesis by facilitating the activities of reactive oxygen species (ROS), NF-κB, and NFATc1 in vitro and prevents the development of OVX-induced osteoporosis mouse models in vivo. Methods. The docking mechanism of DIC and RANKL was initially identified by protein-ligand molecular docking. RNA sequencing was performed and analyzed to reveal the potential mechanism and signaling pathway of the antiosteoporosis effects of DIC. To verify the sequencing results, we examined the impact of DIC on RANKL-induced osteoclast differentiation, bone resorption, F-actin ring production, ROS generation, and NF-κB activation in osteoclasts in vitro. Moreover, a luciferase assay was performed to determine the binding and transcriptional activity of Nrf2 and NF-κB. The in vivo efficacy of DIC was assessed with an ovariectomy- (OVX-) induced osteoporosis model, which was analyzed using micro-CT and bone histomorphometry. Results. The molecular docking results indicated that DIC could bind particularly to RANKL. RNA-seq confirmed that DIC could regulate the osteoclast-related pathway. DIC suppressed osteoclastogenesis, bone resorption, F-actin belt formation, osteoclast-specific gene expression, and ROS activity by preventing NFATc1 expression and affecting NF-κB signaling pathways in vitro. The luciferase assay showed that DIC not only suppressed the activity of Nrf2 but also contributed to the combination of Nrf2 and NF-κB. Our in vivo study indicated that DIC protects against OVX-induced osteoporosis and preserves bone volume by inhibiting osteoclast activity and function. Conclusions. DIC can ameliorate osteoclast formation and OVX-induced osteoporosis and therefore is a potential therapeutic treatment for osteoporosis.

Chemical space docking enables large-scale structure-based virtual screening to discover ROCK1 kinase inhibitors

With the ever-increasing number of synthesis-on-demand compounds for drug lead discovery, there is a great need for efficient search technologies. We present the successful application of a virtual screening method that combines two advances: (1) it avoids full library enumeration (2) products are evaluated by molecular docking, leveraging protein structural information. Crucially, these advances enable a structure-based technique that can efficiently explore libraries with billions of molecules and beyond. We apply this method to identify inhibitors of ROCK1 from almost one billion commercially available compounds. Out of 69 purchased compounds, 27 (39%) have Ki values < 10 µM. X-ray structures of two leads confirm their docked poses. This approach to docking scales roughly with the number of reagents that span a chemical space and is therefore multiple orders of magnitude faster than traditional docking.

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery.

Extracellular vesicles (EVs), including exosomes, mediate intercellular communication by delivering their contents, such as nucleic acids, proteins, and lipids, to distant target cells. EVs play a role in the progression of several diseases. In particular, programmed death-ligand 1 (PD-L1) levels in exosomes are associated with cancer progression. Furthermore, exosomes are being used for new drug-delivery systems by modifying their membrane peptides to promote their intracellular transduction via micropinocytosis. In this review, we aim to show that an efficient drug-delivery system and a useful therapeutic strategy can be established by controlling the molecular docking and intracellular translocation of exosomes. We summarise the mechanisms of molecular docking of exosomes, the biological effects of exosomes transmitted into target cells, and the current state of exosomes as drug delivery systems.

Some Aspects of Party Cooperation between Kazakhstan and China

The article reveals the issues of multifaceted cooperation and development of China and Kazakhstan in the framework of the joint construction of “One Belt, One Road” and the economic policy of Kazakhstan “Nurly Zhol” (“Bright Road”).Aim. Put forward proposals to promote the development of Kazakh-Chinese trade based on a study of the current situation in the development of Kazakh-Chinese relations and cooperation relations within the framework of the “One Belt, One Road” and an analysis of limiting factors.Tasks. Consider the key ideas underlying the two plans, identify the main scope and areas of cooperation, analyze the prospects for the implementation of the international cooperation project and the achievements achieved so far.Methods. To compare the practices of the Silk Road Economic Belt and the Nurly Zhol Plan, a comparative analysis method was adopted to identify the existing advantages and disadvantages of development. The method of bibliographic data analysis was also used in the article. By searching and studying scientific materials and works of domestic and foreign scientists, deepen the understanding of the impact and features of the One Belt, One Road initiative on Kazakhstan.Results. On the basis of specific achievements of cooperation, constructive proposals were put forward for the further development of Chinese-Kazakh cooperation. In order to smoothly promote cooperation between the construction of the Silk Road Economic Belt and the Bright Road, it is necessary to further improve common procedures and docking mechanisms, to fully use the communication capabilities of the SCO to promote economic cooperation.Conclusion. One Belt One Road and Nurly Zhol have achieved strong complementarity. The cooperation between them has satisfied the development needs of Kazakhstan and China. But the security of cooperation requires serious attention. China, Kazakhstan, and even the countries of Central Asia should jointly raise security awareness and deepen cooperation in non-traditional security areas within the framework of the Shanghai Cooperation Organization and deepen the connection between the SCO and other regional security mechanisms.

Design and Analysis of a New Deployable Docking Mechanism for Microsatellites

In-orbit docking technology of microsatellites to realize combined reconfiguration has a wide application prospect, such as large antennas and space telescopes. In order to reduce collision impact and improve docking accuracy, a new deployable docking mechanism is proposed based on the slider-crank principle, which has the advantages of smaller volume and larger posture tolerance. To achieve large capture tolerance and increase the success rate of docking, the posture error is analyzed by considering the specific boundary of the position and pose. And a step-by-step cooperative capture strategy is proposed to complete the velocity selection and action matching among multiple capture arms. The reliable docking of posture correction in the docking process is realized by designing the action path of the docking mechanism. The effects of tolerance capture under different initial posture conditions are analyzed by dynamic simulation. The effectiveness and superiority of the step-by-step cooperative capture strategy are valid by comparison with the synchronized capture strategy. The comparison results show that the impact force is reduced by 8% than the synchronized strategy. The capture experiments are carried out to verify the docking performance. The results show the proposed configuration with a step-by-step cooperative capture strategy achieves successfully reliable capture, weak impact, and large posture tolerance under eight extreme initial pose conditions.

Design, Synthesis, DFT, TD-DFT/PCM Calculations, and Molecular Docking Studies on the Anti-COVID-19, and Anti-SARS Activities of Some New Bis-Thiazoles and Bis-Thiadiazole

A novel synthesis of bis(thiazoles) and bis(thiadiazole), each connected to a thienothiophene moiety, is described. The DFT calculations support the favored synthesis of one of the anticipated bis(thiazole) regioisomers. The B3LYP/6-311G** level of theory was used to optimize quantum mechanical calculations of geometrical characteristics and energy of new compounds under study. The electronic absorption of the new compounds in ethanol solvent was handled and finished using time-dependent-density functional theory (TD-DFT) at the B3LYP/6-31G(d,p) level with the addition of the polarizable continuum solvation technique TD-DFT/PCM. The permissible singlet transitions are identified, and their involvements in the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are described. Natural bond orbital (NBO) analysis was used to investigate hyper conjugative partnerships, molecular stability, and bond strength. Mean polarizability, total static dipole moment, anisotropy of polarizability, and mean first-order hyperpolarizability have all been computed. The results reveal that the compounds are promising contenders for non-linear optical materials. The molecular docking mechanism between ligands 8a–8c and COVID-19/5epw or SARS/5wrg receptors was done to explore the binding modes of these compounds at the active sites. Molecular docking results have shown that the compounds 8a–8c can be considered as a potential agent against COVID-19/5epw and SARS/5wrg receptors.

A four parallel laser-based simultaneous measurement method for 6-degrees-of-freedom errors of rigid body with translational motion.

The measurement of six-degrees-of-freedom (6-DOF) errors of rigid bodies can show the real and accurate spatial pose of those rigid bodies. It plays a major role in precision calibration, spacecraft docking, machining, assembly, etc. In this paper, a four parallel laser-based simultaneous measurement (FPL-SM) method is proposed for measuring 6-DOF errors of rigid bodies with translational motion. First, a FPL-SM device is introduced. Its four laser heads form a rectangle, which is perpendicular to the movement direction of the measured linear displacement. Second, identification formulas for all geometrical errors in rigid bodies with translational motion are presented based on the relative positions of the four lasers. Based on the readings of the four lasers, angular errors and corresponding straightness errors are calculated for the direction of motion around the other two linear motions. As the two parallel sides of the rectangle are in different planes, the straightness errors of the two planes are different. The rolling angular error in the direction is expressed as the difference between the straightness errors of the two planes divided by the distance between the two planes. Six fundamental errors for rigid bodies with translational motion are obtained by four lasers in a single setting of the device. For multiple rigid bodies with mutually perpendicular translational motion, the squareness error is calculated by fitting to the actual direction of motion. Finally, experiments were carried out on the SmartCNC_DRDT five-axis machine tool and 21 geometric errors were determined for three translational axes. Error compensation was carried out using the generated machine tool geometric error data to verify the effectiveness of the proposed FPL-SM method. In addition, geometric errors and thermal errors of the Z axis of the GTI-2740 machine tool are measured based on the FPL-SM method.