Kinematic Flexibility Analysis: Hydrogen Bonding Patterns Impart a Spatial Hierarchy of Protein Motion

Elastic network models (ENM) and constraint-based, topological rigidity analysis are two distinct, coarse-grained approaches to study conformational flexibility of macromolecules. In the two decades since their introduction, both have contributed significantly to insights into protein molecular mechanisms and function. However, despite a shared purpose of these approaches, the topological nature of rigidity analysis, and thereby the absence of motion modes, has impeded a direct comparison. Here, we present an alternative, kinematic approach to rigidity analysis, which circumvents these drawbacks. We introduce a novel protein hydrogen bond network spectral decomposition, which provides an orthonormal basis for collective motions modulated by non-covalent interactions, analogous to the eigenspectrum of normal modes, and decomposes proteins into rigid clusters identical to those from topological rigidity. Our kinematic flexibility analysis bridges topological rigidity theory and ENM, and enables a detailed analysis of motion modes obtained from both approaches. Our analysis reveals that collectivity of protein motions, reported by the Shannon entropy, is significantly lower for rigidity theory versus normal mode approaches. Strikingly, kinematic flexibility analysis suggests that the hydrogen bonding network encodes a protein-fold specific, spatial hierarchy of motions, which goes nearly undetected in ENM. This hierarchy reveals distinct motion regimes that rationalize protein stiffness changes observed from experiment and molecular dynamics simulations. A formal expression for changes in free energy derived from the spectral decomposition indicates that motions across nearly 40% of modes obey enthalpy-entropy compensation. Taken together, our analysis suggests that hydrogen bond networks have evolved to modulate protein structure and dynamics

Modelling of Electromechanical Coupling in Geometrically Exact Beam Dynamics

Dielectric elastomers show promising performance as actuators for soft robotics. Thus, accurate and efficient numerical algorithms for the simulation of Dielectric Elastomer Actuators (DEAs) are required for the design and control of the soft robotic system. In this work, the Cosserat formulation of geometrically exact beam dynamics is extended by adding the electric potential as an additional degree of freedom to account for the electrical effects. A formulation of electric potential and electric field for the geometrically exact beam model is proposed such that complex beam deformations can be generated by the electrical forces. The kinematic variables in continuum electromechanics are formulated in terms of beam strains. The electromechanically coupled constitutive model for the beam formulation is obtained by integrating the strain energy in continuum electromechanics over the beam cross section, which leads to a direct transfer of the dielectric constitutive models in continuum mechanics to the beam model. The electromechanically coupled beam dynamics is solved with a variational time integrator scheme. By applying different electrical boundary conditions to the beam nodes, different deformation modes of the beam are obtained in the numerical example

A multirate variational approach to simulation and optimal control for flexible spacecraft

We propose an optimal control method for simultaneous slewing and vibration control of flexible spacecraft. Considering dynamics on different time scales, the optimal control problem is discretized on micro and macro time grids using a multirate variational approach. The description of the system and the necessary optimality conditions are derived through the discrete Lagrange-d'Alembert principle. The discrete problem retains the conservation properties of the continuous model and achieves high fidelity simulation at a reduced computational cost. Simulation results for a single-axis rotational maneuver demonstrate vibration suppression and achieve the same accuracy as the single rate method at reduced computational cost.Comment: This paper was presented at the 2020 AAS/AIAA Astrodynamics Specialist Conferenc

Interaction of the Mechano-Electrical Feedback With Passive Mechanical Models on a 3D Rat Left Ventricle: A Computational Study

In this paper, we are investigating the interaction between different passive material models and the mechano-electrical feedback (MEF) in cardiac modeling. Various types of passive mechanical laws (nearly incompressible/compressible, polynomial/exponential-type, transversally isotropic/orthotropic material models) are integrated in a fully coupled electromechanical model in order to study their specific influence on the overall MEF behavior. Our computational model is based on a three-dimensional (3D) geometry of a healthy rat left ventricle reconstructed from magnetic resonance imaging (MRI). The electromechanically coupled problem is solved using a fully implicit finite element-based approach. The effects of different passive material models on the MEF are studied with the help of numerical examples. It turns out that there is a significant difference between the behavior of the MEF for compressible and incompressible material models. Numerical results for the incompressible models exhibit that a change in the electrophysiology can be observed such that the transmembrane potential (TP) is unable to reach the resting state in the repolarization phase, and this leads to non-zero relaxation deformations. The most significant and strongest effects of the MEF on the rat cardiac muscle response are observed for the exponential passive material law

Homogenization of the constitutive properties of composite beam cross-sections

When modelling slender bodies made of composite materials as beams, homogenized stiffness coefficients must be obtained. In [2, 3], analytic expressions for these are obtained by comparing the solutions of some Saint-Venant extension, bending and torsion 3D linear elasticity problems with their corresponding beam theory counterparts. In [2], the authors provide general expressions for the determination of these coefficients for multilayered beams. The present work consists in the study of a homogenization procedure of the stiffness coefficients for circular cross-sections with two layers. This will help in the study of the constitutive behavior of unloaded shafts of endoscopes since their cross-section could be studied as a simplified model of a three-layers hollow circular cross-section. In preparation of this geometry, results of an experimental campaign carried out at KARL STORZ GmbH & Co. KG (Tallinn, Estonia) are presented in a second part of this paper. The purpose of the testing was the experimental characterization of the torsional stiffness of such devices

Optimal Control Strategies for Robust Certification

We present an optimal control methodology, which we refer to as concentration-of-measure optimal control (COMOC), that seeks to minimize a concentration-of-measure upper bound on the probability of failure of a system. The systems under consideration are characterized by a single performance measure that depends on random inputs through a known response function. For these systems, concentration-of-measure upper bound on the probability of failure of a system can be formulated in terms of the mean performance measure and a system diameter that measures the uncertainty in the operation of the system. COMOC then seeks to determine the optimal controls that maximize the confidence in the safe operation of the system, defined as the ratio of the design margin, which is measured by the difference between the mean performance and the design threshold, to the system uncertainty, which is measured by the system diameter. This strategy has been assessed in the case of a robot-arm maneuver for which the performance measure of interest is assumed to be the placement accuracy of the arm tip. The ability of COMOC to significantly increase the design confidence in that particular example of application is demonstrated

Discrete Adjoint Method for Variational Integration of Constrained ODEs and its application to Optimal Control of Geometrically Exact Beam Dynamics

Direct methods for the simulation of optimal control problems apply a specific discretization to the dynamics of the problem, and the discrete adjoint method is suitable to calculate corresponding conditions to approximate an optimal solution. While the benefits of structure preserving or geometric methods have been known for decades, their exploration in the context of optimal control problems is a relatively recent field of research. In this work, the discrete adjoint method is derived for variational integrators yielding structure preserving approximations of the dynamics firstly in the ODE case and secondly for the case in which the dynamics is subject to holonomic constraints. The convergence rates are illustrated by numerical examples. Thirdly, the discrete adjoint method is applied to geometrically exact beam dynamics, represented by a holonomically constrained PDE.Comment: Funding: H2020 Marie-Sk\l{}odowska-Curie 86012

On optimal control simulations for mechanical systems

The primary objective of this work is the development of robust, accurate and efficient simulation methods for the optimal control of mechanical systems, in particular of constrained mechanical systems as they appear in the context of multibody dynamics. The focus is on the development of new numerical methods that meet the demand of structure preservation, i.e. the approximate numerical solution inherits certain characteristic properties from the real dynamical process. This task includes three main challenges. First of all, a kinematic description of multibody systems is required that treats rigid bodies and spatially discretised elastic structures in a uniform way and takes their interconnection by joints into account. This kinematic description must not be subject to singularities when the system performs large nonlinear dynamics. Here, a holonomically constrained formulation that completely circumvents the use of rotational parameters has proved to perform very well. The arising constrained equations of motion are suitable for an easy temporal discretisation in a structure preserving way. In the temporal discrete setting, the equations can be reduced to minimal dimension by elimination of the constraint forces. Structure preserving integration is the second important ingredient. Computational methods that are designed to inherit system specific characteristics – like consistency in energy, momentum maps or symplecticity – often show superior numerical performance regarding stability and accuracy compared to standard methods. In addition to that, they provide a more meaningful picture of the behaviour of the systems they approximate. The third step is to take the previ- ously addressed points into the context of optimal control, where differential equation and inequality constrained optimisation problems with boundary values arise. To obtain meaningful results from optimal control simulations, wherein energy expenditure or the control effort of a motion are often part of the optimisation goal, it is crucial to approxi- mate the underlying dynamics in a structure preserving way, i.e. in a way that does not numerically, thus artificially, dissipate energy and in which momentum maps change only and exactly according to the applied loads. The excellent numerical performance of the newly developed simulation method for optimal control problems is demonstrated by various examples dealing with robotic systems and a biomotion problem. Furthermore, the method is extended to uncertain systems where the goal is to minimise a probability of failure upper bound and to problems with contacts arising for example in bipedal walking