Determining the Orientation of Protegrin-1 in DLPC Bilayers Using an Implicit Solvent-Membrane Model

Continuum models that describe the effects of solvent and biological membrane molecules on the structure and behavior of antimicrobial peptides, holds a promise to improve our understanding of the mechanisms of antimicrobial action of these peptides. In such methods, a lipid bilayer model membrane is implicitly represented by multiple layers of relatively low dielectric constant embedded in a high dielectric aqueous solvent, while an antimicrobial peptide is accounted for by a dielectric cavity with fixed partial charge at the center of each one of its atoms. In the present work, we investigate the ability of continuum approaches to predict the most probable orientation of the β-hairpin antimicrobial peptide Protegrin-1 (PG-1) in DLPC lipid bilayers by calculating the difference in the transfer free energy from an aqueous environment to a membrane-water environment for multiple orientations. The transfer free energy is computed as a sum of two terms; polar/electrostatic and non-polar. They both include energetic and entropic contributions to the free energy. We numerically solve the Poisson-Boltzmann equation to calculate the electrostatic contribution to the transfer free energy, while the non-polar contribution to the free energy is approximated using a linear solvent accessible surface area relationships. The most probable orientation of PG-1 is that with the lowest relative transfer free energy. Our simulation results indicate that PG-1 assumes an oblique orientation in DLPC lipid bilayers. The predicted most favorable orientation was with a tilt angle of 19°, which is in qualitative agreement with the experimentally observed orientations derived from solid-state NMR data

Network Theory Analysis of Antibody-Antigen Reactivity Data: The Immune Trees at Birth and Adulthood

Motivation: New antigen microarray technology enables parallel recording of antibody reactivities with hundreds of antigens. Such data affords system level analysis of the immune system’s organization using methods and approaches from network theory. Here we measured the reactivity of 290 antigens (for both the IgG and IgM isotypes) of 10 healthy mothers and their term newborns. We constructed antigen correlation networks (or immune networks) whose nodes are the antigens and the edges are the antigen-antigen reactivity correlations, and we also computed their corresponding minimum spanning trees (MST) – maximal information reduced sub-graphs. We quantify the network organization (topology) in terms of the network theory divergence rate measure and rank the antigen importance in the full antigen correlation networks by the eigen-value centrality measure. This analysis makes possible the characterization and comparison of the IgG and IgM immune networks at birth (newborns) and adulthood (mothers) in terms of topology and node importance. Results: Comparison of the immune network topology at birth and adulthood revealed partial conservation of the IgG immune network topology, and significant reorganization of the IgM immune networks. Inspection of the antigen importance revealed some dominant (in terms of high centrality) antigens in the IgG and IgM networks at birth, which retain their importance at adulthood

Organization of the autoantibody repertoire in healthy newborns and adults revealed by system level informatics of antigen microarray data

The immune system is essential to body defense and maintenance. Specific antibodies to foreign invaders function in body defense, and it has been suggested that autoantibodies binding to self molecules are important in body maintenance. Recently, the autoantibody repertoires in the bloods of healthy mothers and their newborns were studied using an antigen microarray containing hundreds of self molecules. It was found that the mothers expressed diverse repertoires for both IgG and IgM autoantibodies. Each newborn shares with its mother a similar repertoire of IgG antibodies, which cross the placental but its IgM repertoire is more similar to those of other newborns. Here, we took a system-level approach and analyzed the correlations between autoantibody reactivities of the previous data and extended the study to new data from newborns at birth and a week later, and from healthy young women. For the young women, we found modular organization of both IgG and IgM isotypes into antigen cliques—subgroups of highly correlated antigen reactivities. In contrast, the newborns were found to share a universal congenital IgM profile with no modular organization. Moreover, the IgG autoantibodies of the newborns manifested buds of the mothers' antigen cliques, but they were noticeably less structured. These findings suggest that the natural autoantibody repertoire of humans shows relatively little organization at birth, but, by young adulthood, it becomes sorted out into a modular organization of subgroups (cliques) of correlated antigens. These features revealed by antigen microarrays can be used to define personal states of autoantibody organizational motifs

Vulnerability of network of networks

Our dependence on networks – be they infrastructure, economic, social or others – leaves us prone to crises caused by the vulnerabilities of these networks. There is a great need to develop new methods to protect infrastructure networks and prevent cascade of failures (especially in cases of coupled networks). Terrorist attacks on transportation networks have traumatized modern societies. With a single blast, it has become possible to paralyze airline traffic, electric power supply, ground transportation or Internet communication. How, and at which cost can one restructure the network such that it will become more robust against malicious attacks? The gradual increase in attacks on the networks society depends on – Internet, mobile phone, transportation, air travel, banking, etc. – emphasize the need to develop new strategies to protect and defend these crucial networks of communication and infrastructure networks. One example is the threat of liquid explosives a few years ago, which completely shut down air travel for days, and has created extreme changes in regulations. Such threats and dangers warrant the need for new tools and strategies to defend critical infrastructure. In this paper we review recent advances in the theoretical understanding of the vulnerabilities of interdependent networks with and without spatial embedding, attack strategies and their affect on such networks of networks as well as recently developed strategies to optimize and repair failures caused by such attacks