Protein flexibility and dynamics using constraint theory

A new approach is presented for determining the rigid regions in proteins and the flexible joints between them. The short-range forces in proteins are modeled as constraints and we use a recently developed formalism from graph theory to analyze flexibility in the bond network. Forces included in the analysis are the covalent bond-stretching and bond-bending forces, salt bridges, and hydrogen bonds. We use a local function to associate an energy with individual hydrogen bonds, which then can be included or excluded depending on the bond strength. Colored maps of the rigid and flexible regions provide a direct visualization of where the motion of the protein can take place, consistent with these distance constraints. We also define a flexibility index that quantifies the local density of flexible or floppy modes, in terms of the dihedral angles that remain free to rotate in each flexible region. A negative flexibility index provides a measure of the density of redundant bonds in rigid regions. A new application of this approach is to simulate the maximal range of possible motions of the flexible regions by introducing Monte Carlo changes in the free dihedral angles, subject to the distance constraints. This is done using a method that maintains closure of the rings formed by covalent and hydrogen bonds in the flexible parts of the protein, and van der Waals overlaps between atoms are avoided. We use the locus of the possible motions of HIV protease as an example: movies of its motion can be seen at http://www.pa.msu.edu/~lei.     

Analysis of the domain interactions between the protease and helicase of NS3 in dengue and hepatitis C virus

Flaviviridae non-structural 3 protein (NS3) is a multifunctional enzyme, composed by a protease domain (NS3pro) and an RNA helicase domain (NS3hel). The activities present in NS3 have proved to be critical for viral replication. The replicative cycle of Flaviviridae requires coordinated regulation of all the activities present in the full-length NS3 protein, however, the exact nature of these interactions remains unclear. The present work aimed to determine common structural features between NS3 of dengue and hepatitis C viruses and to characterize residues involved in the regulation of the interdomain motions between NS3pro and NS3hel. Analysis of the root mean square (RMS) variation shows that NS3pro increases the stability of subdomain 1 of the RNA helicase. Moreover, the dynamic behaviour of the carboxy terminus of NS3hel, supports the hypothesis that, upon release of the carboxy-terminus from NS3pro, the residues involved in this interaction are folded back into the last alpha-helix. Using normal mode analysis, we characterized slow collective motions of NS3, and observed that the two lowest-frequency normal modes are enough to describe reorientations of NS3pro relative to NS3hel. These movements induced an increment in the exposure of the active site of NS3pro that can be important during the proteolytic processing of the viral polyprotein. The third low-frequency normal mode was correlated to subdomain reorientations of NS3hel, similar to those proposed during NTP hydrolysis and dsRNA unwinding. Based on these data, we support a dynamic model, in which the domain movements between NS3pro and NS3hel result in the regulation of its activities.     

Dynamics of a rotating flexible and symmetric spacecraft using impedance matrix in terms of the flexible appendages cantilever modes

The subject of this work is the dynamics of a rotating spacecraft. The spacecraft is modeled as a main rigid body connected to two flexible solar panels. The orbital motion of the whole spacecraft with a constant angular velocity is considered, interacting with small rigid motions of the main body, and small elastic deformations and infinitesimal vibrations of the solar panels. A continuum approach based on the Rayleigh–Ritz discretization is used to describe the distributed flexibility in the spacecraft. Rayleigh–Ritz discretization functions used are the clamped modes of the solar panels. This method enables us to construct the impedance matrix of the whole system relating to the displacement of the main body and the external torque. A spectral expansion of this impedance matrix, in terms of these clamped modes is obtained in the frequency domain. The numerical results presented show that for small values of orbital angular velocity, the vibration motion frequencies of the flexible parts (solar panels) are not perturbed substantially. Moreover, when great values of orbital angular velocity are simulated, these frequencies change considerably. The present investigation based on the Rayleigh–Ritz discretization shows the effect of the interaction between the orbital motion of the whole spacecraft and the vibration motions of the flexible parts.     

Extraction and analysis of multiple periodic motions in video sequences

The analysis of periodic or repetitive motions is useful in many applications, such as the recognition and classification of human and animal activities. Existing methods for the analysis of periodic motions first extract motion trajectories using spatial information and then determine if they are periodic. These approaches are mostly based on feature matching or spatial correlation, which are often infeasible, unreliable, or computationally demanding. In this paper, we present a new approach, based on the time- frequency analysis of the video sequence as a whole. Multiple periodic trajectories are extracted and their periods are estimated simultaneously. The objects that are moving in a periodic manner are extracted using the spatial domain information. Experiments with synthetic and real sequences display the capabilities of this approach.     

大变形柔性管道两相流流致振动研究

针对柔性管道内段塞流引起的结构大变形流致振动问题,本文采用分区强流固耦合方法建立了面向大变形两相流输运管道的双向流固耦合数值计算模型.基于流体体积法对气液两相流动界面进行追踪并结合任意拉格朗日-欧拉(ALE)动网格方法考虑流体域网格变形,同时采用有限元方法建立了柔性管道动力学模型,根据流体和管道壁面的相互作用构建强流固耦合计算模型.研究表明,在两相流作用下柔性管道的振动主要以类似一阶和二阶振动模态响应为主且会发生模态切换;模态切换与管内的液塞长度、液塞流动频率以及气液塞在管内的轴向分布有关;管道的大变形振动促进了短气塞的融合并显著改变了液塞的长度和频率,进而影响管道的振动和流型转变界限.     

Control of laparoscopic instrument motion in an inanimate bench model: implications for the training and the evaluation of technical skills

Computer-assisted analysis of wrist movement has recently emerged as an objective laparoscopic performance evaluation method. The first purpose of this study was to assess the differences in motion characteristics between the tip of the instrument and the wrist. The second purpose was to describe the control strategies used to move laparoscopic instruments. During a bead transfer task, motions of a laparoscopic needle driver's tip, heel, and the participants' wrist were monitored. Results showed that large amplitude movements were best described by movements of the wrist, and small amplitude movements were evidenced by motions of the instrument tip. Thus, for describing expertise, and for evaluation and feedback, motion of the tip of the laparoscopic instrument should be quantified, in addition to motion of the wrist. The motions of the instrument were controlled by utilizing the flexibility of the skin of the laparoscopic trainer in addition to using the fulcrum, and sliding through the trocar. In order to increase fidelity, virtual reality trainers should simulate the flexibility of the real structures around the insertion of the instrument.     

Effects of load and speed on lumbar vertebral kinematics during lifting motions

This experimental study investigated the effects of load magnitude and movement speed on lumbar vertebral kinematics during lifting task performance. Ten participants performed sagittally symmetric lifting movements with systematically varied load using either a normal or a faster-than-normal speed. Skin-surface markers were strategically placed over the participants' spinous processes and other landmarks representing major body joints and were recorded during the movements by a motion capture system. The center of rotation (COR) locations and segmental movement profiles for lumbar vertebrae L2 to L5 were derived and analyzed. Results suggested that (a) the COR locations and vertebral angular displacement were not significantly affected by the speed or load variation; (b) a faster speed tended to shorten the time to complete the acceleration for all the lumbar vertebrae considered; and (c) the load increase incurred a tendency for the L5 to complete the primary displacement in a briefer time while enduring greater peak acceleration and velocity. The findings lead to a better understanding of the relation between lifting dynamics and spinal motion. Potential applications of this research include the development of more accurate biomechanical models and software tools for depicting spinal motions and quantifying low-back stress.     

On simulating human reach motions for ergonomics analyses

Many existing job analysis tools for ergonomics have concentrated on the potential adverse effects of force, posture, and repetition, as these appear to be traditionally recognized risk factors in the workplace. Recent investigations have indicated that this pragmatic approach may be overly simplistic, and thus miss prediction of risk factors associated with certain motions. This article reviews some of the research under way in the University of Michigan's Human Motion Simulation Laboratory to develop a set of human motion prediction models. To produce these models, over 37,000 motions of 100 men and women from 18 to 78 years in age have been measured with a motion capture system. The motions are typical of people reaching and moving light to moderate load objects while either seated or standing. A 17‐link kinematics model has been developed to resolve the dynamics of the motions. Thus far, initial motion algorithms have been developed that capture well over 95% of the between participant repeatability. Advantages and limitations of the methods and data being used are discussed and illustrated. © 2002 Wiley Periodicals, Inc.     

Muscular synergy classification and myoelectric control using high-order cross-cumulants

High-order statistics (HOS) are well suited for describing non-Gaussian random processes. These techniques are increasingly being employed in myoelectric research, on both time and frequency domain techniques. This work presents HOS-based techniques using only HOS time domain features to classify myoelectric signals. The auto-, cross- and full- (joint) third-order cumulants are evaluated as EMG-signal feature vectors to be compared between them. Four surface EMG signals were processed for classify motions from the upper limbs. Synergy among channels is characterized by the features in both auto and cross modes, and their incidences for classifying five or six movements are analyzed. In contrast to the third-order auto-cumulants, it had been verified that the third-order cross-cumulants have the same classification rate by working with five or six movements. A myoelectric control scheme and its experimental application were executed with normal and disabled subjects, reaching a classification rates of 90%, in average. Accuracy in online experiments was similar to the off-line classification rate.

     

Prediction of the receptor conformation for iGluR2 agonist binding: QM/MM docking to an extensive conformational ensemble generated using normal mode analysis

Highly flexible proteins constitute a significant challenge in molecular docking within the field of drug design. Depending on the efficacy of the bound ligand, the ligand-binding domain (LBD) of the ionotropic glutamate receptor iGluR2 adopts markedly different degrees of domain closure due to large-scale domain movements. With the purpose of predicting the induced domain closure of five known iGluR2 partial to full agonists we performed a validation study in which normal mode analysis (NMA) was employed to generate a 25-membered ensemble of iGluR2 LBD structures with gradually changing domain closures, followed by accurate QM/MM docking to the ensemble. Based on the docking scores we were able to predict the correct optimal degree of closure for each ligand within 1–3° deviation from the experimental structures. We demonstrate that NMA is a useful tool for reliable ensemble generation and that we are able to predict the ligand induced conformational change of the receptor through docking to such an ensemble. The described protocol expands and improves the information that can be obtained from computational docking when dealing with a flexible receptor.     

Prediction of the receptor conformation for iGluR2 agonist binding: QM/MM docking to an extensive conformational ensemble generated using normal mode analysis

Highly flexible proteins constitute a significant challenge in molecular docking within the field of drug design. Depending on the efficacy of the bound ligand, the ligand-binding domain (LBD) of the ionotropic glutamate receptor iGluR2 adopts markedly different degrees of domain closure due to large-scale domain movements. With the purpose of predicting the induced domain closure of five known iGluR2 partial to full agonists we performed a validation study in which normal mode analysis (NMA) was employed to generate a 25-membered ensemble of iGluR2 LBD structures with gradually changing domain closures, followed by accurate QM/MM docking to the ensemble. Based on the docking scores we were able to predict the correct optimal degree of closure for each ligand within 1–3° deviation from the experimental structures. We demonstrate that NMA is a useful tool for reliable ensemble generation and that we are able to predict the ligand induced conformational change of the receptor through docking to such an ensemble. The described protocol expands and improves the information that can be obtained from computational docking when dealing with a flexible receptor.     

Two methods for the computation of nonlinear modes of vibrating systems at large amplitudes

The aim of this paper is to present two methods for the calculation of the nonlinear normal modes of vibration for undamped nonlinear mechanical systems: the time integration periodic orbit method and the modal representation method. In the periodic orbit method, the nonlinear normal mode is obtained by making the continuation of branches of periodic orbits of the equation of motion. The terms “periodic orbits” means a closed trajectory in the phase space, which is obtained by time integration. In the modal representation method, the nonlinear normal mode is constructed in terms of amplitude, phase, mode shape, and frequency, with the distinctive feature that the last two quantities are amplitude and total phase dependent. The methods are compared on two DOF strongly nonlinear systems.     

鱼类群体运动的元胞自动机模型中的最小势能原理

群体运动是自然界中一种常见的生物行为. 在一定的环境条件下, 社会有机体会表现出不同的集体运动形态. 其中, 旋转是鱼群中常见的群体运动. 但是, 虽然研究人员对鱼群的运动进行过一系列的研究, 这种旋转行为的机理尚不清楚. 本研究假定鱼群的运动模式受势能的支配, 相应提出了鱼类个体运动的势函数并将之融合到元胞自动机中以模拟鱼群的运动. 数值模拟表明, 有限空间内鱼群运动时会形成多种形状, 但当此生物系统按照能量最小原则发展时, 其运动形态最终可能演化成为一个漩涡. 数值模拟与针对红斑马鱼的观察之间的比较验证了本模型的合理性. 能量最小原理是自然界的基本定律之一, 而势能函数的建立定义了鱼类个体与环境之间的关系. 因此, 本研究为深入理解群体运动规律提供了新视角, 表明从流体力学上进一步探究鱼群运动的物理机理是一个具有潜力的研究方向.     

Chattering analysis in sliding mode systems with inertial sensors

Singularly perturbed relay control systems with second order sliding modes (SP2SM) are considered for modeling of sliding mode control systems with inertial sensors. It is shown that the asymptotically stable slow-motion integral manifold of a smooth singularly perturbed system, describing the motion of an original SP2SM in the second order sliding domain, is the asymptotically stable slow-motions integral manifold of the original SP2SM. For sliding mode control systems with inertial sensors sufficient conditions for the exponential decreasing of the amplitude of chattering and unlimited growth of frequency are found. A formula for asymptotic representation of 'ideal' switching surface oscillations is suggested for sliding mode systems with inertial sensors.     

Visualization of combined motions in human joints

Relationships between joint pathology and kinematics are well known in orthopedics, though generally they remain unquantified: painful joints may exhibit abnormal motion and, vice versa, chronic nonphysiological motions may lead to joint pathology. Presently, orthopedic therapists have no tool that allows them to simultaneously visualize joint morphology and joint kinematics. This article presents a novel technique to improve visualization of the motions of human joints and the variable relationships between the joint segments during their displacement     

视频监控系统中基于MPEG编码域的运动检测方法

运动检测是视频监控系统中极有实用价值的技术，该文简单介绍了MPEG编码的基本特征，并利用这些特征在编码域中进行运行检测，提出了一种利用运动矢量进行运动检测的方法，该方法不但能检测出运动，还能区分出摄像头和物体的运动，并判断运动类型。     

Video repairing under variable illumination using cyclic motions

This paper presents a complete system capable of synthesizing a large number of pixels that are missing due to occlusion or damage in an uncalibrated input video. These missing pixels may correspond to the static background or cyclic motions of the captured scene. Our system employs user-assisted video layer segmentation, while the main processing in video repair is fully automatic. The input video is first decomposed into the color and illumination videos. The necessary temporal consistency is maintained by tensor voting in the spatio-temporal domain. Missing colors and illumination of the background are synthesized by applying image repairing. Finally, the occluded motions are inferred by spatio-temporal alignment of collected samples at multiple scales. We experimented on our system with some difficult examples with variable illumination, where the capturing camera can be stationary or in motion.     

Unsteady RANS method for ship motions with application to roll for a surface combatant

An unsteady Reynolds-averaged Navier-Stokes method is developed to compute motions and the resulting flow and wave fields around surface ships. Although the formulation and RANS code are generalized for six-degree-of-freedom motions, the method is demonstrated here for the viscous phenomenon of roll decay motion for a surface combatant. The method is based on an extension of CFDSHIP-IOWA (a general-purpose code for computational ship hydrodynamics) to predict ship motions with larger amplitude and non-slender geometry, in comparison to traditional linearized methods. The flow solver uses higher-order upwind discretization, PISO method for pressure-velocity coupling, a blended k-ω/k-ε two-equation turbulence model, free surface tracking approach, and structured multi-block grid systems. As an initial step, unsteady simulations of a modern surface combatant with predicted roll decay and prescribed sinusoidal roll motion are performed. Roll decay motion is simulated by releasing the model from an initial roll angular displacement and by computing the resulting roll motion. Verification of the time history of the roll motion is performed using iteration, grid, and time step studies and numerical uncertainties are shown to be less than 1%. Validation is performed by comparison with available experimental data with the predictions validated at 1.7% and 1.5% for the uncorrected and corrected solutions, respectively. For simulations with prescribed motions, the periodic response of the boundary layer to the rolling motion is described and quantified using a Fourier analysis. A spring-mass-damper system is used to compare the current non-linear predictions to traditional linear strip theory results. The method is shown to accurately predict the natural rolling frequency and roll decay rate at multiple ship speeds both without and with bilge keels, which demonstrates the ability to assess seakeeping characteristics for practical geometries.     

带柔性天线卫星机动过程动力学分析

基于刚柔耦合动力学模型仿真分析卫星机动过程的动力学特性.模型将天线上的柔性金属网近似成阻尼弹簧模型,将径向肋刚化并等效其柔性为径向肋根部的扭簧转角;利用该简化模型研究了卫星机动过程中径向肋和金属网的柔性对卫星姿态的影响.通过仿真分析天线卫星系统在不同结构参数情况以及不同驱动力作用下的卫星机动过程动力学特性,对比分析得出：提高径向肋的固有频率,增加金属网以及增大径向肋扭簧的阻尼能有效降低刚柔耦合问题对卫星本体姿态的影响.     

Stochastic Dynamics: Simulating the Effects of Turbulence on Flexible Structures

This paper addresses the problem of realistically simulating the motion of tree-branches subjected to turbulence. Since the resulting motion is random in nature, we model it as a stochastic process. We synthesize this process directly by filtering a white noise in the Fourier domain. The filter is constructed by performing a modal analysis of the tree. We use a sophisticated numerical technique which is able to compute the first few significant modes of large trees. The main advantage of our technique over previous methods is that we are able to compute complicated motions without the necessity of integrating dynamical equations over time. Consequently, a user can view and manipulate tree-motions in real-time. Our technique can be further extended to other flexible structures such as two-dimensional plates.