Automated Generation of Explicit Port-Hamiltonian Models from Multi-Bond Graphs

Port-Hamiltonian system theory is a well-known framework for the control of complex physical systems. The majority of port-Hamiltonian control design methods base on an \emph{explicit} input-state-output port-Hamiltonian model for the system under consideration. However in the literature, little effort has been made towards a systematic, automatable derivation of such explicit models. In this paper, we present a constructive, formally rigorous method for an explicit port-Hamiltonian formulation of multi-bond graphs. Two conditions, one necessary and one sufficient, for the existence of an explicit port-Hamiltonian formulation of a multi-bond graph are given. We summarise our approach in a fully automated algorithm of which we provide an exemplary implementation along with this publication. The theoretical and practical results are illustrated through an academic example

Explicit port-Hamiltonian formulation of bond graphs with dependent storages

Explicit port-Hamiltonian systems (PHSs) are the starting point for many powerful controller and observer design methods. It is well-known that explicit PHSs can be formulated on the basis of bond graphs. Indeed, the port-Hamiltonian formulation of bond graphs without dependent storages has been well investigated. However, little effort has been made towards bond graphs with dependent storages. This is a problem as dependent storages frequently occur in models from many engineering fields. In this paper, we address the explicit port-Hamiltonian formulation of bond graphs with dependent storages. Our idea is to express the port-Hamiltonian dynamics and output as functions of only the system inputs and independent storages. The main result is a rigorous and constructive method to formulate bond graphs containing dependent storages as explicit PHSs. An acadamic example illustrates and verifies our method

Morphing of Amphipathic Helices to Explore the Activity and Selectivity of Membranolytic Antimicrobial Peptides

Naturally occurring membranolytic antimicrobial peptides (AMPs) are rarely cell-type selective and highly potent at the same time. Template-based peptide design can be used to generate AMPs with improved properties de novo. Following this approach, 18 linear peptides were obtained by computationally morphing the natural AMP Aurein 2.2d2 GLFDIVKKVVGALG into the synthetic model AMP KLLKLLKKLLKLLK. Eleven of the 18 chimeric designs inhibited the growth of Staphylococcus aureus, and six peptides were tested and found to be active against one resistant pathogenic strain or more. One of the peptides was broadly active against bacterial and fungal pathogens without exhibiting toxicity to certain human cell lines. Solution nuclear magnetic resonance and molecular dynamics simulation suggested an oblique-oriented membrane insertion mechanism of this helical de novo peptide. Temperature-resolved circular dichroism spectroscopy pointed to conformational flexibility as an essential feature of cell-type selective AMPs.ISSN:0006-2960ISSN:1520-499

Morphing of Amphipathic Helices to Explore the Activity and Selectivity of Membranolytic Antimicrobial Peptides

Naturally occurring membranolytic antimicrobial peptides (AMPs) are rarely cell-type selective and highly potent at the same time. Template-based peptide design can be used to generate AMPs with improved properties de novo. Following this approach, 18 linear peptides were obtained by computationally morphing the natural AMP Aurein 2.2d2 GLFDIVKKVVGALG into the synthetic model AMP KLLKLLKKLLKLLK. Eleven of the 18 chimeric designs inhibited the growth of Staphylococcus aureus, and six peptides were tested and found to be active against one resistant pathogenic strain or more. One of the peptides was broadly active against bacterial and fungal pathogens without exhibiting toxicity to certain human cell lines. Solution nuclear magnetic resonance and molecular dynamics simulation suggested an oblique-oriented membrane insertion mechanism of this helical de novo peptide. Temperature-resolved circular dichroism spectroscopy pointed to conformational flexibility as an essential feature of cell-type selective AMPs.ISSN:0006-2960ISSN:1520-499

Peptide–Membrane Interaction between Targeting and Lysis

Certain cationic peptides interact with biological membranes. These often-complex interactions can result in peptide targeting to the membrane, or in membrane permeation, rupture, and cell lysis. We investigated the relationship between the structural features of membrane-active peptides and these effects, to better understand these processes. To this end, we employed a computational method for morphing a membranolytic antimicrobial peptide into a nonmembranolytic mitochondrial targeting peptide by “directed simulated evolution.” The results obtained demonstrate that superficially subtle sequence modifications can strongly affect the peptides’ membranolytic and membrane-targeting abilities. Spectroscopic and computational analyses suggest that N- and C-terminal structural flexibility plays a crucial role in determining the mode of peptide–membrane interaction