Molecular dynamics simulation of force-regulated interaction between glycoprotein Ib α and filamin / 生物医学工程学杂志

In resting platelets, the 17 th domain of filamin a (FLNa17) constitutively binds to the platelet membrane glycoprotein Ibα (GPIbα) at its cytoplasmic tail (GPIbα-CT) and inhibits the downstream signal activation, while the binding of ligand and blood shear force can activate platelets. To imitate the pull force transmitted from the extracellular ligand of GPIbα and the lateral tension from platelet cytoskeleton deformation, two pulling modes were applied on the GPIbα-CT/FLNa17 complex, and the molecular dynamics simulation method was used to explore the mechanical regulation on the affinity and mechanical stability of the complex. In this study, at first, nine pairs of key hydrogen bonds on the interface between GPIbα-CT and FLNa17 were identified, which was the basis for maintaining the complex structural stability. Secondly, it was found that these hydrogen bonding networks would be broken down and lead to the dissociation of FLNa17 from GPIbα-CT only under the axial pull force; but, under the lateral tension, the secondary structures at both terminals of FLNa17 would unfold to protect the interface of the GPIbα-CT/FLNa17 complex from mechanical damage. In the range of 0~40 pN, the increase of pull force promoted outward-rotation of the nitrogen atom of the 563 rd phenylalanine (PHE 563-N) at GPIbα-CT and the dissociation of the complex. This study for the first time revealed that the extracellular ligand-transmitted axial force could more effectively relieve the inhibition of FLNa17 on the downstream signal of GPIbα than pure mechanical tension at the atomic level, and would be useful for further understanding the platelet intracellular force-regulated signal pathway.

Semi-rational evolution of ω-transaminase from Aspergillus terreus for enhancing the thermostability / 生物工程学报

ω-transaminase (ω-TA) is a natural biocatalyst that has good application potential in the synthesis of chiral amines. However, the poor stability and low activity of ω-TA in the process of catalyzing unnatural substrates greatly hampers its application. To overcome these shortcomings, the thermostability of (R)-ω-TA (AtTA) from Aspergillus terreus was engineered by combining molecular dynamics simulation assisted computer-aided design with random and combinatorial mutation. An optimal mutant AtTA-E104D/A246V/R266Q (M3) with synchronously enhanced thermostability and activity was obtained. Compared with the wild- type (WT) enzyme, the half-life t1/2 (35 ℃) of M3 was prolonged by 4.8-time (from 17.8 min to 102.7 min), and the half deactivation temperature (T1050) was increased from 38.1 ℃ to 40.3 ℃. The catalytic efficiencies toward pyruvate and 1-(R)-phenylethylamine of M3 were 1.59- and 1.56-fold that of WT. Molecular dynamics simulation and molecular docking showed that the reinforced stability of α-helix caused by the increase of hydrogen bond and hydrophobic interaction in molecules was the main reason for the improvement of enzyme thermostability. The enhanced hydrogen bond of substrate with surrounding amino acid residues and the enlarged substrate binding pocket contributed to the increased catalytic efficiency of M3. Substrate spectrum analysis revealed that the catalytic performance of M3 on 11 aromatic ketones were higher than that of WT, which further showed the application potential of M3 in the synthesis of chiral amines.

Integrated

The drug formulation design of self-emulsifying drug delivery systems (SEDDS) often requires numerous experiments, which are time- and money-consuming. This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches. 4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods. Random forest (RF) showed the best prediction performance with 91.3% for accuracy, 92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation. The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy (89.51%). The central composite design (CCD) was used to screen the best ratio of oil-surfactant-cosurfactant. Finally, molecular dynamic (MD) simulation was used to investigate the molecular interaction between excipients and drugs, which revealed the diffusion behavior in water and the role of cosurfactants. In conclusion, this research combined machine learning, central composite design, molecular modeling and experimental approaches for rational SEDDS formulation design. The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.

Discovery of human coronaviruses pan-papain-like protease inhibitors using computational approaches / 药物分析学报

The papain-like protease (PLpro) is vital for the replication of coronaviruses (CoVs), as well as for escaping innate-immune responses of the host. Hence, it has emerged as an attractive antiviral drug-target. In this study, computational approaches were employed, mainly the structure-based virtual screening coupled with all-atom molecular dynamics (MD) simulations to computationally identify specific inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro, which can be further developed as potential pan-PLpro based broad-spectrum antiviral drugs. The sequence, structure, and functional con-serveness of most deadly human CoVs PLpro were explored, and it was revealed that functionally important catalytic triad residues are well conserved among SARS-CoV, SARS-CoV-2, and middle east respiratory syndrome coronavirus (MERS-CoV). The subsequent screening of a focused protease in-hibitors database composed of ～7,000 compounds resulted in the identification of three candidate compounds, ADM_13083841, LMG_15521745, and SYN_15517940. These three compounds established conserved interactions which were further explored through MD simulations, free energy calculations, and residual energy contribution estimated by MM-PB(GB)SA method. All these compounds showed stable conformation and interacted well with the active residues of SARS-CoV-2 PLpro, and showed consistent interaction profile with SARS-CoV PLpro and MERS-CoV PLpro as well. Conclusively, the re-ported SARS-CoV-2 PLpro specific compounds could serve as seeds for developing potent pan-PLpro based broad-spectrum antiviral drugs against deadly human coronaviruses. Moreover, the presented infor-mation related to binding site residual energy contribution could lead to further optimization of these compounds.

Mutant P21 Peptides Could Act As An Improved Cyclin A Inhibitors For Cancer Therapy: An In Silico Validation

Objective: The present study delineates the generation of mutant peptide library from a known anticancer peptide, p21 and in silico evaluation for their affinity towards cyclin. A substrate binding groove. Methods: Mutant peptide library was created based on their AntiCP score and was docked with cyclin A using ClusPro2.0 web server. The docked structures were further simulated into an aqueous environment using Gromacs 4.5.6. Visualization was performed using PyMol software and interaction analysis was done using Discovery Studio Visualizer 4.1 Client and LigPlot plus tool. Results: A total of 57 mutant peptides were generated; out of which only 3 namely, K3C (Lys3Cys), K3F (Lys3Phe), and K3W (Lys3Trp) had a greater affinity for cyclin A than WILD p21 peptide (HSKRRLIFS). Molecular dynamic simulation studies showed that the peptides remained docked into the substrate binding groove throughout the run. Among all the peptides, K3C showed a significantly higher negative binding energy with cyclin A as compared to WILD. Conclusion: The overall results suggested that K3C mutant peptide had ~30 % higher affinity towards cyclin A and thus, could further be explored for its anticancer potential. The study also provides an insight into the crucial interactions governing the recognition of substrate binding groove of cyclin A for the development of novel peptide-based anticancer therapeutics.

Dynamic simulation and experimental verification of human body turning over in supine position / 生物医学工程学杂志

The tilted supine position has been evaluated to be one of the significantly effective approaches to prevent bedsore of the patients in the bedridden state. Thus, it has deeply positive influences that in view of dynamics this study explores how the position works. Based on the anatomical theories, this study formulates the human dynamic model. Furthermore, the dynamic simulation of three usual postures in tilted supine position including lying on back, lying with one knee bent and lying with the upper and lower limb on one side lifted is carried out. Therefore, the changes of the three driving forces named as chest force, waist force and thigh force in the tilted supine position can be observed. In order to verify the validity of this simulation, this study obtains the electromyogram measurements of ectopectoralis, external obliques and thigh muscles which are respectively close to the chest, waist and thigh by conducting the human force measurements experiment. The result revealed that in terms of range and trend, the experimental data and simulation's data were consistent. In conclusion, the changes of these muscles in the supine position movements are researched efficiently by both this experiment and the dynamic simulation. Besides, the result is crucially key to find the mechanism of human's tilted supine position movements.

A numerical dynamic simulation study of licorice concentration process / 中草药

Objective Taking the concentration process of liquorice extract as the research object, the dynamic simulation process of concentration of Chinese materia medica (CMM) was constructed by combining experimental analysis with theoretical simulation, which provided the model support and theoretical analysis basis for the process research and equipment development of concentration process of CMM. Methods The corresponding relationship between boiling point and saturated vapor pressure of liquorice solution was determined by dynamic method. The experimental data were fitted by thermodynamic model to obtain relevant parameters. On this basis, the simulation process of liquorice water extract concentration was constructed by using ASPEN PLUS. According to the simulation of dynamic process, the effects of heating power, feed rate, and vacuum degree on liquorice solution concentration process in an external thermal concentrator were discussed. Finally, the equations about concentration time and heating power were obtained by simulation. Results The results of parameter fitting were Aij = 1.63, Aji = 2.32, Bij = 336.38, Bji = 792.00, and Cij = 0.5. Finally, the functional equation for the concentration time and heating power was t = 2 329 c1H/c0Q. Conclusion In this study, the effects of different process parameters on the concentration process of TCM were analyzed by simulation and related theories, and a simple prediction of the concentration process was realized. It also perfected and optimized the process simulation data, filled the relevant scientific research gap, and was of great significance to industrial guidance. Firstly, the relevant experimental data was obtained by fitting the thermodynamic model with the relevant experimental data. Then, under the ideal process conditions, the influencing factors of liquorice concentration process were analyzed and discussed by dynamic simulation. It was concluded that heating power was the key factor affecting the concentration process, and the concentration time gradually decreased with the increase of heating power. However, their functional relationship was non-linear. At the same time, the functional equation can be used to roughly predict the concentration time of CMM. To a certain extent, this fills in the gap between the related theoretical research and data of chemical thermodynamics, which provides theoretical support for the process research and equipment development of the concentration process of CMM.

Numerical Study on the Effect from Nitric Oxide on Regulation of Pulmonary Vascular in Different Pulmonary Ventilation Conditions / 医用生物力学

Objective To study the changes of nitric oxide (NO) concentration in arterial-capillary-venous vessels and the dynamic regulation mechanism of NO on the vessels during ventilation changes. Method The pulmonary vascular network model was established by using the COMSOL Multiphysics software, the dynamic regulation of NO on blood vessels was introduced, the flow-multiphysics coupling simulation was conducted to explore the effect of oxygen and blood flow on NO concentration and its distribution in pulmonary vascular network, and the dynamic regulation of NO on pulmonary vascular function in the case of ventilation lacking. Results Oxygen concentration and blood flow would jointly affect the NO distribution in the pulmonary vascular network. When lung ventilation was insufficient, the amount of oxygen entering the pulmonary capillaries decreased, and the NO concentration in pulmonary vein walls under static conditions was significantly reduced. The reduction of NO concentration under dynamic conditions led to vasoconstriction and decrease of blood vessel radius, resulting a dynamic compensation. Regulation of vascular tension regulation coefficient α would directly affect the regulation of NO. When α worked within a certain range, a higher value of α meant a larger change in vascular radius and a smaller change in NO concentration, and its effective value was greater than 1. Conclusions The research findings revealed the change of NO concentration in arterial-capillary-venous vessels due to the change of ventilation as well as the dynamic regulation mechanism of NO in blood vessels, and predicted the effective value range of α，thus providing theoretical basis for further research on the mechanism of blood flow, ventilation perfusion ratio affected by vasoconstriction and vascular resistance changes due to ventilation insufficiency.

Investigation of the influence of mechanical signals on the structure of CD44/FERM complex via molecular dynamics simulation / 生物医学工程学杂志

The intracellular domain of clusters of differentiation 44 (CD44) binding to the FERM (protein 4.1-ezrin-radixin-moesin) domain of ERM (ezrin/radixin/moesin) proteins and furthermore triggering the recruitment of spleen tyrosine kinase (Syk) are very important in the process of tumor cell adhesion, migration and proliferation. At first, it was found that CD44/FERM structure was stable by observing CD44/FERM complex conformation and analyzing the interaction of interface residues both in static crystal structure and in equilibrium process. Meanwhile, unconventional immunoreceptor tyrosine-based activation motif (ITAM-like), and phosphorylation sites Y191 and Y205 were buried in FERM domain, which would hinder the phosphorylation of ERM proteins, the recruitment of Syk and subsequent signal transduction. Then, steered molecular dynamics simulation was applied to simulate the interaction between CD44 and FERM domain in the mechanical environment. The results showed that mechanical signal could induce the exposure of the ITAM-like motif and phosphorylation site Y205 by tracking and analyzing CD44/FERM complex conformational changes and the solvent-accessible surface area. This study revealed how the force regulates the activation of downstream signal through CD44 intracellular domain for the first time, and would be useful for further understanding the adhesion and migration pathway of cancer cells and the design of antitumor drugs.

Structural Study on K-Segment of Rice Dehydrin in Mimetic Membrane / 分析化学

Dehydrins are well associated with the abiotic stress tolerance of the plants, such as dehydration, salt stress and cold stress. They include a highly conserved lysine-rich motif called K-segment, which is believed to play a significant role in dehydrin function. The K-segment shows in vitro antibacterial activity against Gram-positive bacteria like its full-length dehydrin protein. In this study, the structures of the K-segment from rice dehydrin have been investigated by CD spectroscopy, NMR and molecular dynamic simulation. The results reveal that the K-segment is disordered in aqueous solution, but adopts helical structure in mimetic membrane environment, sodium dodecyl sulfate (SDS) micelles. The central region of K-segment forms an a-helix and exhibits amphipathic arrangement,where hydrophobic residues locate on one side and hydrophilic residues are on the other side. The amphipathic feature allows the helix region of the K-segment to insert into the SDS micelles, resulting in stable association with mimetic membrane. To realize the energy minimization,the hydrophobic side of the helix faces to the hydrophobic core of SDS micelles,and the hydrophilic side of the helix faces to the surface of micelles. The precise 3D structure and orientation information of the K-segment obtained in this work might provide new insights in understanding the structure-function relationship of dehydrins.

Structure based virtual screening, docking and molecular dynamic simulation studies to identify potent mdm2-p53 inhibitors: Future implications for cancer therapy

Objective: To identify the p53 binding pocket as well as active residues in mdm2 protein, and search for similar (or) better compounds to inhibit mdm2-p53 interactions in comparison to FDA approved drug (Nutlin) by ligand and structure based virtual screening methods, docking, and molecular dynamic simulation studies. Methods: A structure and ligand based virtual screening for mdm2 protein; targeting the key residues involved in their active binding of p53 peptide was conducted after obtaining structurally suitable compounds similar to Nutlin from ZINC database. These compounds are virtually screened onto the mdm2 protein targeting its active binding site where p53 binds. The best compound with highest binding affinity was taken up for further analysis using molecular dynamic simulations for further validating the docking studies and to reveal interactions during the conformational changes Results: We discovered several compounds that are potentially able to block the interaction between active residues of mdm2 and p53 complex, suggesting their capability to act as anti-cancer agents. As proven by our structure based virtual screening studies coupled with semi-flexible and flexible docking studies, compound ZINC59256947 was found to be the strongest inhibitors for mdm2 protein amongst all of those isolates from ZINC database. Conclusion: Our results suggest that, a simple, selective and reliable inhibition assay can be performed to search for novel inhibitors of p53-mdm2 interaction. Therefore this study provides a rationalization to the ability of a ZINC59256947, an isolate from ZINC database with strong binding affinity towards mdm2 protein, for future implications as anti-cancer agent.

Dynamic simulation analysis of effects of project of ditching for drain on On-comelania hupensis snail control and flood prevention security in Dongting Lake region / 中国血吸虫病防治杂志

Objective To evaluate the effects of the project of ditching for drain on Oncomelania hupensis snail control and flood prevention security and explore the optimal engineering design plan in Dongting Lake region. Methods A retrospective study was performed on the previous studies about the project of ditching for drain. The reference values of project indices were determined. The outside levee of Nanhu New Distinct of Yueyang City in Dongting Lake region was selected as the study area , and the cross section of marshland perpendicular to the center line of the levee was extracted to research. According to the situa?tions of various water levels,a dynamic simulation was performed on the effect and security of the project of ditching for drain through the software FLAC3D. Results The retrospective study showed that the project would be effective when the relatively subsoil water level decreased by 0.35 m,and the soil water content decreased correspondingly. The dynamic simulation by FLAC3D showed that the minimum safe distances between transverse ditch 1,vertical ditch and levee toe should be 25 m and 13 m respectively. The digging depth of transverse ditch and vertical ditch should be 1.2 m and 1.0 m respectively. If the width of marshland in drought period was less than 500 m,one transverse ditch was efficient. Otherwise,more transverse ditches should be set with the intervals of 300 m. Conclusions The project of ditching for drain is an effective ecological snail elimination method. Optimizing the digging depth of ditches and distances between transverse ditches,vertical ditch and levee toe will en?sure the effects and security of the project.

A preliminary study of binding site on β-tubulin interacting with the new anti-cancer drug docetaxel / 国际生物医学工程杂志

Objective To study the interaction mechanism of anti-cancer drug docetaxel (DTX) andβ-tubulin, to determine the binding sites and the involved amino acids between the β-tubulin and docetaxel, and to analyze the dynamic combination process. Methods The docking binding energy and interaction sites of DTX molecules withβ-tubulin on the potential energy surface were calculated by molecular docking method. The dynamic interaction process of the low binding energy DTX with β-tubulin was simulated by molecular dynamics method. Results The results of molecular docking showed that there are three interaction sites, including N1, N2 and N3, between DTX and β-tubulin. The DTX molecules with structure of No.1, 2 and 4, which have excellent docking energy, were chose for molecular dynamics simulation. As a result, the dynamic change processes of the system complexes from non-equilibrium to equilibrium were obtained. The simulation results showed that the hydrogen bonds formed by the DTX with structure No.1 were significantly higher than those with structures No. 2 and 4. The solvent accessibility surface area of the DTX with structures No.1, 2 and 4 was higher than that of paclitaxel. Conclusion The model of DTX binding toβ-tubulin was established, which could provide theoretical guidance for the design and development of novel paclitaxel anticancer drugs.

Análisis dinámico de la capacidad de respuesta de una cadena de suministros de productos tecnológicos. Caso Samsung

Se presentan los resultados de la simulación de una cadena de suministro de productos tecnológicos, orientado a la flexibilidad de producción desde una perspectiva de capacidad de respuesta en un contexto de producción bajo pedido. Se caracteriza la cadena de suministros identificando los elementos que constituyen el sistema para la formulación del caso de estudio y modelo dinámico, el cual es programado, calibrado y analizado en Vensim DSS. Los resultados reflejan que incrementos en la demanda implican ampliaciones en la capacidad de la planta a una tasa determinada por una política de mejora, condicionando la respuesta de la cadena. En las primeras etapas, la capacidad está por debajo de la demanda; en la fase de declive, gran parte de las instalaciones quedan ociosas; además, elementos como el tiempo de procesamiento, tiempo de entrega y tipo de orden son factores determinantes en la respuesta de la cadena. Más aún, la exactitud de los pronósticos para anticipar aumentos inesperados en la demanda contribuye a mejorar la respuesta de la cadena. Se concluye que el comportamiento de los productos tecnológicos crea grandes dificultades en la gestión de las cadenas de este tipo, dado que su obsolescencia y rápido crecimiento requieren que los eslabones de la cadena generen una respuesta sincronizada e inmediata, con el propósito de obtener un alto nivel de servicio. Sin embargo, esto implica inversiones significativas.

In this paper are presented the results of the simulation of a supply chain of technology products, aimed at production flexibility from the perspective of responsiveness in the context make to order Supply Chain is characterized by identifying the elements that constitute the system for the development of the case study and dynamic model, which is programmed, calibrated and analyzed in Vensim DSS. The results show that an increase in demand, implies expansion of the capacity of the plant at a rate determined by a policy of improving, conditioning the response of the chain. In the early stages, the capacity is below demand; but the decline phase, most of the facilities are idle. Additional, elements such as processing time, delivery time and insertion order are determining factors in the response chain. Furthermore, the accuracy of forecasts anticipate unexpected increases in demand that helps to improve the response chain. In conclusion, the behavior of technology products creates great difficulties in managing chains such as its obsolescence and rapid growth requires that the links in the chain generate a synchronized and immediate response in order to obtain a high level of service. However this involves significant investment.

Os resultados da simulação de uma tecnologia de cadeia de fornecimento flexibilidade de produção orientada para o produto a partir de um ponto de vista da capacidade de resposta em um pedido de contexto de produção apresentado. cadeia de fornecimento é caracterizado por identificar os elementos do sistema para a formulação de estudo de caso e o modelo dinâmico, que é programado, calibrado e analisado em DSS Vensim. Os resultados mostram que o aumento da procura envolvem a expansão da capacidade da planta a uma taxa determinada por uma política de melhoramento, condicionado a cadeia de resposta. Nos estágios iniciais, a capacidade é inferior à procura; na fase de declínio, a maioria das instalações estão ociosos; elementos adicionais, tais como o tempo de processamento, tempo de entrega eo tipo de ordem são fatores determinantes na cadeia de resposta. Além disso, a precisão das previsões para antecipar aumentos inesperados na demanda contribui para melhorar a cadeia de resposta. Concluiu-se que o comportamento de produtos de tecnologia cria grandes dificuldades na administração de cadeias deste tipo, uma vez que a sua caducidade e rápido crescimento requerem elos de corrente gerar uma resposta sincronizado e imediato, de modo a obter um elevado nível de serviço. No entanto, isso envolve um investimento significativo.

Biomechanical study on the impact injure of human mandible by finite element method / 实用口腔医学杂志

Objective:To investigate biomechanical changes of mandible in the impact injure simulated by finite element method (FEM).Methods:Mimics and Comsol software were used to build a FEM of human craniofacial bone based on CT scan data of a normal adult.LS-DYNA and Hypermesh software were used to simulate the impact with different quality,velocity and angulation pro-duced injures of human mandible,the biomechanical parameters of the mandible in the impact injury process were analysed.Results:A FEMof human maxillofacial bone was established,and the dynamic process of different impact force produced damage was simula-ted.Mandibular chin,angle and condylar neck was the stress concentrated area in the process of mandible injury.There was higher stress peak at the site which was closer to the impact position,the stress peak arrival time was also earlier.When the impactor with the same quality,the bigger the velocity,the greater the stress peak.When the impactor with the same velocity,the bigger the quali-ty,the greater the stress peak.When the impactor with the same velocity and quality,there was greater stress peak under the impact to mandible from angulation of 0 degree.Stress transfered to the surrounding bone from the impact position radially and gradually re-duced.The bone area with small cross-section was prone to high stress and more serious damage.Conclusion:The quality,the ve-locity,the impact angle and the impact site are the factors affecting the severity of impact injury.

Analyzing resistance pattern of non-small cell lung cancer to crizotinib using molecular dynamic approaches.

Crizotinib is the potential anticancer drug used for the treatment of non-small cell lung cancer (NSCLC) approved by FDA in 2011. The main target for the crizotinib is anaplastic lymphoma kinase (ALK). Evidences available indicate that double mutant ALK (L1196M and G1269A) confers resistance to crizotinib. However, how mutation confers drug resistance is not well-understood. Hence, in the present study, molecular dynamic (MD) simulation approach was employed to study the impact of crizotinib binding efficacy with ALK structures at a molecular level. Docking results indicated that ALK double mutant (L1196M and G1269A) significantly affected the binding affinity for crizotinib. Furthermore, MD studies revealed that mutant ALK-crizotinib complex showed higher deviation, higher fluctuation and decreased number of intermolecular H-bonds, when compared to the native ALK-crizotinib complex. These results may be immense importance for the molecular level understanding of the crizotinib resistance pattern and also for designing potential drug molecule for the treatment of lung cancer.

Study of Simulation Application of Simulink Pharmacokinetic Compartment Model / 中国药师

Objective:To dynamically describe the drug concentration change in different time in vivo to understand the in vivo be-havior patterns and rules of drugs, provide reference for performing individual treatment and avoiding adverse drug reactions and lay foundation for dynamic description of physiological pharmacokinetic model. Methods:A two-compartment model was established using Simulink dynamic simulation and used in curve fitting and parameter estimation. The results from the model were compared with those from 3P97 software. Results:There was no significant difference between the results from the dynamic model and those from 3P97 soft-ware. Conclusion:The dynamic model can be used to dynamically simulate two-compartment model for oral administration. The re-sults from the dynamic simulation are more direct, and can correct the fitting error in 3P97 software.

Inverse dynamics simulation on lower limb responses of badminton athlete under impact loads / 医用生物力学

Objective To analyze the badminton athletes’dynamic responses in their lower limbs under impact loads. Methods A human musculoskeletal model was established based on AnyBody Modeling System software and verified by measuring surface electromyography (EMG). The muscle force, joint force, joint torque of lower limbs during right Front-Court Lunge Step in badminton were studied by inverse dynamic simulation and analysis through Vicon motion capture system and force platform. Results The musculoskeletal model was validated to be effective by EMG. During right Front-Court Lunge Step in badminton，the force peak of the hip and ankle joint in Z direction was larger than that in X and Y direction, and the force peak of the knee joint in X direction was larger than that in Y and Z direction. During buffer period, the hip joint in X, Y, Z direction showed adduction, extension and internal rotation torque, respectively, the knee joint in X, Y, Z direction showed abduction, flexion and external rotation torque, respectively, and the ankle joint in X, Y direction showed varus and plantar flexion torque, respectively. The peak torque of the hip, knee and ankle joint in X direction was significantly larger than that in Y and Z direction. Vastus lateralis, biceps femoris, anterior tibial and medial gastrocnemius played a larger role against the ground reaction, while rectus femoris, semitendinosus, soleus played a relatively smaller role against the ground reaction. Conclusions The established musculoskeletal model in the study can provide a technical platform to analyze athletes’biomechanical properties of lower limbs under impact loads. To avoid sport injuries, more attention should be paid to the effect from ground reaction force load at touchdown instant on hip, knee and ankle joints in anteroposterior and mediolateral direction during footwork similar to Front-Court Lunge Step in badminton, and at the same time, the strength training of vastus lateralis, biceps femoris, anterior tibial and medial gastrocnemius of badminton players should not be ignored during specialized training.

Simulation on dynamic characteristics of the ankle gait simulator and experimental verification / 医用生物力学

Objective To study dynamic characteristics of the ankle gait simulator, simulate plantar forces in the vertical, anterior-posterior, right-left direction during the stance phase, and validate such forces in the experimental setup. Methods The Adams virtual prototype and ankle model (including tendons, ligaments and soft tissues of foot) were established for dynamic simulation based on the self-developed 5 DOF gait simulator. The dynamic results from both the prototype and gait simulator were compared with the real plantar forces. Results The simulated plantar force could accurately fit the normal in vivo ankle position curves during a stance phase in three directions, and the tendons, ligaments and soft tissues had important influences on the correct gait. The simulated plantar force by the gait simulator could be repeatedly fit for the real stance plantar force. Conclusions The gait simulator was proved to simulate the human gait stance well and can provide a clinical research platform for those experiments which are incapable of in vivo measurement.

Transient dynamic analysis and optimization of a new customized lingual self-locking appliance during occluding / 医用生物力学

Objective To study the characteristics of stress distributions on a customized lingual self-locking orthodontic appliance under transient occlusal force and optimize its structure. Methods A whole 3D model including denture, appliances and wire was established by CT scanning, reverse engineering method and CAD technology; transient nonlinear dynamic analysis on this model during occluding and its structural optimization were conducted, and the optimized lingual appliance was made based on rapid prototyping technology to verify reliability of the finite element model. Results The equivalent stress on the bracket bottom was larger than that on other parts of the bracket; the maximum equivalent stress on the bracket cover was decreased by 60.9% after installing a reinforcing rib on it, which could effectively prevent stress concentration caused by the contact between the arch wire and bracket cover. The simulation results fundamentally agreed with the loading experiment on the bracket cover. Conclusions For lingual orthodontic treatment in clinic, the relative position between interaction points of the occlusal force and brackets should be concerned so as to avoid impairing the self-locking function; through optimizing the appliance design, the elastic potential energy of arch wire can be transferred more effectively to the teeth and reduce losses of the orthodontic force.