Human motions result from a complex and well-coordinated interaction between the body segments. Walking and the sit-to-stand transfer are amongst the most challenging human motion in terms of coordination and internal loads, respectively. We propose model-based nonlinear optimal control methods to reconstruct and synthesize these motions while considering the dynamics of the motion over the whole time horizon. The redundant and highly nonlinear character of the computed motions encourages to discretize the optimization problem according to direct multiple-shooting methods. The goal is to identify principles which enable us to describe the patterns of these motions.
We approach human walking from the perspective of unimpaired subjects and subjects walking with unilateral transfemoral prostheses. Their walking motion is reconstructed from motion capture data using subject-specific threedimensional multibody models. The motion of the models is fitted to the recorded data for a whole stride in a least-squares sense in multi-stage optimal control problems. Analyzing the reconstructed motion for the individual foot placement of the subjects suggests that it relates with the Capturability concept: foot locations are chosen by the subjects which enable a balance between the inherently conflicting goals of effortless progression and quick response to perturbations. In addition, the modulation of the ground collision impact forces at heel strike is found to play a major role in the step-by-step stability strategy. Based on these findings, we propose Capturability as a complementary criterion to the established clinical stability assessment methods.
The sit-to-stand motion is particularly demanding for humans with mobility impairments, due to the high joint loads required to lift the body into the standing pose. We synthesize optimal sit-to-stand by solving two-stage optimal control problems. We presume that the sit-to-stand motion is substantially characterized by a preparation phase prior to the actual lift-off. Full body models are established with dynamic model parameters which specifically represent elderly humans from different levels of mobility. For impaired subjects, mobility support is assumed to be provided by generic support actions. The optimization computations result in different patterns which include significant arm motion in both phases. Therefore, the results support our approach to choose a full body representation of the human as well as to consider two stages in the optimal control problem.
The computation of optimal assisted sit-to-stand motions of impaired humans offers the opportunity to optimize design parameters for mobility assistance devices providing adequate support. Based on the support actions for the sit-to-stand motions computed for two different levels of impairment, optimal mechanical design parameters for two different sit-to-stand assistance devices are generated. Our approach to separate the human-device interaction at their interface ensures that the optimal support provided to the human by the device is not compromised by any dynamic coupling between them. Solving large-scale nonlinear optimal control problems with multiple stages, we obtain design parameters for the devices which are optimal in terms of the workspace and the mechanical effort required.
Computational methods can help to better understand and analyze the interaction of proteins and their binding partners. This interaction is influenced by many factors, including specific sequence variants, the dynamics and electrostatics of the proteins, as well as further physicochemical properties of the corresponding binding partners. A detailed investigation of these different, and often complicated, properties helps to better understand the functionality of proteins, for which the interaction with other molecules plays a crucial role. The work presented here provides new methodologies, implemented in webservers and software, which assist during the analysis of proteins. Furthermore, in an application case, computational methods and analyses in combination with experimental results were used to detect a specific interaction network of proteins. The new ProSAT+ webserver enables the visualization of protein sequence annotations in the context of the three–dimensional protein structure and contains additional options for visualizing and sharing protein annotations. The sequence information allows an easy, but extensive analysis of proteins. The functionality of the ProSAT+ webserver can be integrated into other webservers, which was done in the case of the two other webservers for the analysis of protein binding pockets described here. A tool for the LigDig webserver was developed that provides the comparison of protein binding pockets by the alignment and visualization of the binding pockets based on an existing algorithm. The new TRAPP webserver assists in the analysis of protein binding pocket dynamics. The existing TRAPP software was used, and a user web interface was implemented to simplify the usability. Additional new functionalities were also developed, such as the visualization of protein sequence conservation in context of all other TRAPP results in the three–dimensional structure. This allows the detection of conserved or non–conserved regions inside the binding pocket, which might influence the dynamics of the pocket. This newly gained information can be used during the process of designing selective inhibitors. During the protein disaggregation process, members from different classes of the so-called J–protein (HSP40) co–chaperones play a crucial role. The synergetic application of different computational methods and experiments enabled the detection of an interclass specific J–protein interaction and indicated that the interaction evolved to enable a high efficiency in the disaggregation process. The resulting data of performed protein domain docking simulations required an update of the standard clustering workflow. This new methodology can be applied for protein docking in cases that have problems with multiple, weakly specific interaction sites. The work presented here facilitates in many ways the analysis of proteins, including their structure and sequence features, as well as, their dynamics and interactions with their binding partners. The new methods are provided as webservers and therefore are accessible, and easy to use for all researchers. This can assist in many research projects and provide relevant information. The analyses of the J–proteins improved the knowledge about their biological role and functionality, and therefore provide an important contribution for a better understanding of the overall protein disaggregation process.