Influence of the interaction potential on simulated sputtering and reflection data

The TRIM.SP program which is based on the binary collision approximation was changed to handle not only repulsive interaction potentials, but also potentials with an attractive part. Sputtering yields, average depth and reflection coefficients calculated with four different potentials are compared. Three purely repulsive potentials (Meliere, Kr-C and ZBL) are used and an ab initio pair potential, which is especially calculated for silicon bombardment by silicon. The general trends in the calculated results are similar for all potentials applied, but differences between the repulsive potentials and the ab initio potential occur for the reflection coefficients and the sputtering yield at large angles of incidence.

Biomolecular interaction analysis in functional proteomics

In der funktionellen Proteomforschung werden bekannte Interaktionen eines zellulären Netzwerkes qualitativ untersucht. Diese Veröffentlichung beschreibt verschiedene biomolekulare Interaktionsanalysen, anhand des Modellsystems PKA, die zur detaillierten Charakterisierung von Bindungen herangezogen werden können. Neben den Gleichgewichtsbindungsdaten (generiert aus AlphaScreen, FP, SPR und ITC Messungen) wurden aus ITC Messungen die thermodynamischen Parameter G, H und S ermittelt. Durch Anwendung der BRET2 (Bioluminescence resonance energy transfer) Methode konnten in lebenden Zellen Aussagen über Bindungsereignisse und deren Lokalisation getroffen werden.

Protein Folding Simulations: Confinement, External Fields and Sequence Design

The present Thesis looks at the problem of protein folding using Monte Carlo and Langevin simulations, three topics in protein folding have been studied: 1) the effect of confining potential barriers, 2) the effect of a static external field and 3) the design of amino acid sequences which fold in a short time and which have a stable native state (global minimum). Regarding the first topic, we studied the confinement of a small protein of 16 amino acids known as 1NJ0 (PDB code) which has a beta-sheet structure as a native state. The confinement of proteins occurs frequently in the cell environment. Some molecules called Chaperones, present in the cytoplasm, capture the unfolded proteins in their interior and avoid the formation of aggregates and misfolded proteins. This mechanism of confinement mediated by Chaperones is not yet well understood. In the present work we considered two kinds of potential barriers which try to mimic the confinement induced by a Chaperon molecule. The first kind of potential was a purely repulsive barrier whose only effect is to create a cavity where the protein folds up correctly. The second kind of potential was a barrier which includes both attractive and repulsive effects. We performed Wang-Landau simulations to calculate the thermodynamical properties of 1NJ0. From the free energy landscape plot we found that 1NJ0 has two intermediate states in the bulk (without confinement) which are clearly separated from the native and the unfolded states. For the case of the purely repulsive barrier we found that the intermediate states get closer to each other in the free energy landscape plot and eventually they collapse into a single intermediate state. The unfolded state is more compact, compared to that in the bulk, as the size of the barrier decreases. For an attractive barrier modifications of the states (native, unfolded and intermediates) are observed depending on the degree of attraction between the protein and the walls of the barrier. The strength of the attraction is measured by the parameter $\epsilon$. A purely repulsive barrier is obtained for $\epsilon=0$ and a purely attractive barrier for $\epsilon=1$. The states are changed slightly for magnitudes of the attraction up to $\epsilon=0.4$. The disappearance of the intermediate states of 1NJ0 is already observed for $\epsilon =0.6$. A very high attractive barrier ($\epsilon \sim 1.0$) produces a completely denatured state. In the second topic of this Thesis we dealt with the interaction of a protein with an external electric field. We demonstrated by means of computer simulations, specifically by using the Wang-Landau algorithm, that the folded, unfolded, and intermediate states can be modified by means of a field. We have found that an external field can induce several modifications in the thermodynamics of these states: for relatively low magnitudes of the field ($<2.06 \times 10^8$ V/m) no major changes in the states are observed. However, for higher magnitudes than ($6.19 \times 10^8$ V/m) one observes the appearance of a new native state which exhibits a helix-like structure. In contrast, the original native state is a $\beta$-sheet structure. In the new native state all the dipoles in the backbone structure are aligned parallel to the field. The design of amino acid sequences constitutes the third topic of the present work. We have tested the Rate of Convergence criterion proposed by D. Gridnev and M. Garcia ({\it work unpublished}). We applied it to the study of off-lattice models. The Rate of Convergence criterion is used to decide if a certain sequence will fold up correctly within a relatively short time. Before the present work, the common way to decide if a certain sequence was a good/bad folder was by performing the whole dynamics until the sequence got its native state (if it existed), or by studying the curvature of the potential energy surface. There are some difficulties in the last two approaches. In the first approach, performing the complete dynamics for hundreds of sequences is a rather challenging task because of the CPU time needed. In the second approach, calculating the curvature of the potential energy surface is possible only for very smooth surfaces. The Rate of Convergence criterion seems to avoid the previous difficulties. With this criterion one does not need to perform the complete dynamics to find the good and bad sequences. Also, the criterion does not depend on the kind of force field used and therefore it can be used even for very rugged energy surfaces.

Optimization-Based Robotic Manipulation for Safe Interaction with Human Operators

This thesis investigates a method for human-robot interaction (HRI) in order to uphold productivity of industrial robots like minimization of the shortest operation time, while ensuring human safety like collision avoidance. For solving such problems an online motion planning approach for robotic manipulators with HRI has been proposed. The approach is based on model predictive control (MPC) with embedded mixed integer programming. The planning strategies of the robotic manipulators mainly considered in the thesis are directly performed in the workspace for easy obstacle representation. The non-convex optimization problem is approximated by a mixed-integer program (MIP). It is further effectively reformulated such that the number of binary variables and the number of feasible integer solutions are drastically decreased. Safety-relevant regions, which are potentially occupied by the human operators, can be generated online by a proposed method based on hidden Markov models. In contrast to previous approaches, which derive predictions based on probability density functions in the form of single points, such as most likely or expected human positions, the proposed method computes safety-relevant subsets of the workspace as a region which is possibly occupied by the human at future instances of time. The method is further enhanced by combining reachability analysis to increase the prediction accuracy. These safety-relevant regions can subsequently serve as safety constraints when the motion is planned by optimization. This way one arrives at motion plans that are safe, i.e. plans that avoid collision with a probability not less than a predefined threshold. The developed methods have been successfully applied to a developed demonstrator, where an industrial robot works in the same space as a human operator. The task of the industrial robot is to drive its end-effector according to a nominal sequence of grippingmotion-releasing operations while no collision with a human arm occurs.