T he importance of electrostatic modeling to biophysics is well established; electrostatics have been shown to influence various aspects of nearly all biochemical reactions. Advances in NMR, x-ray, and cryo-electron microscopy techniques for structure elucidation have drastically increased the size and number of biomolecules and molecular complexes for which coordinates are available. However, although the biophysical community continues to examine macromolecular systems of increasing scale, the computational evaluation of electrostatic properties for these systems is limited by methodology that can handle only relatively small systems, typically consisting of fewer than 50,000 atoms. Despite these limitations, such computational methods have been immensely useful in analyses of the stability, dynamics, and association of proteins, nucleic acids, and their ligands (1-3). Here we describe algorithms that open the way to similar analyses of much larger subcellular structures.One of the most widespread models for the evaluation of electrostatic properties is the Poisson-Boltzmann equation (PBE) (4, 5)a second-order nonlinear elliptic partial differential equation that relates the electrostatic potential ( ) to the dielectric properties of the solute and solvent ( ), the ionic strength of the solution and the accessibility of ions to the solute interior ( 2 ), and the distribution of solute atomic partial charges ( f ). To expedite solution of the equation, this nonlinear PBE is often approximated by the linearized PBE (LPBE) by assuming sinh (x) Ϸ (x). Several numerical techniques have been used to solve the nonlinear PBE and LPBE, including boundary element (6-8), finite element (9-11), and finite difference (12-14) algorithms. However, despite the variety of solution methods, none of these techniques has been satisfactorily applied to large molecular structures at the scales currently accessible to modern biophysical methods. To accommodate arbitrarily large biomolecules, algorithms for solving the PBE must be both efficient and amenable to implementation on a parallel platform in a scalable fashion, requirements that current methods have been unable to satisfy. Although boundary element LPBE solvers provide an efficient representation of the problem domain, they are not useful for the nonlinear problem and have not been applied to the PBE on parallel platforms. Similarly, adaptive finite element methods have shown some success in parallel evaluation of both the LPBE and nonlinear PBE (15), but limitations in current solver technology and difficulty with efficient representation of the biomolecular data prohibits their practical application to large biomolecular systems. Finally, unlike the boundary and finite element techniques, finite difference methods have the advantage of very efficient multilevel solvers (12, 16) and applicability to both the linear and nonlinear forms of the PBE; however, existing parallel finite difference algorithms often require costly interprocessor communication that limits both the n...

Established methods for characterizing proteins typically require physical or chemical modification steps or cannot be used to examine individual molecules in solution. Ionic current measurements through electrolyte-filled nanopores can characterize single native proteins in an aqueous environment, but currently offer only limited capabilities. Here we show that the zeptolitre sensing volume of bilayer-coated solid-state nanopores can be used to determine the approximate shape, volume, charge, rotational diffusion coefficient and dipole moment of individual proteins. To do this, we developed a theory for the quantitative understanding of modulations in ionic current that arise from the rotational dynamics of single proteins as they move through the electric field inside the nanopore. The approach allows us to measure the five parameters simultaneously, and we show that they can be used to identify, characterize and quantify proteins and protein complexes with potential implications for structural biology, proteomics, biomarker detection and routine protein analysis.

Progress towards the integration of technology into living organisms requires electrical power sources that are biocompatible, mechanically flexible, and able to harness the chemical energy available inside biological systems. Conventional batteries were not designed with these criteria in mind. The electric organ of the knifefish Electrophorus electricus (commonly known as the electric eel) is, however, an example of an electrical power source that operates within biological constraints while featuring power characteristics that include peak potential differences of 600 volts and currents of 1 ampere. Here we introduce an electric-eel-inspired power concept that uses gradients of ions between miniature polyacrylamide hydrogel compartments bounded by a repeating sequence of cation- and anion-selective hydrogel membranes. The system uses a scalable stacking or folding geometry that generates 110 volts at open circuit or 27 milliwatts per square metre per gel cell upon simultaneous, self-registered mechanical contact activation of thousands of gel compartments in series while circumventing power dissipation before contact. Unlike typical batteries, these systems are soft, flexible, transparent, and potentially biocompatible. These characteristics suggest that artificial electric organs could be used to power next-generation implant materials such as pacemakers, implantable sensors, or prosthetic devices in hybrids of living and non-living systems.

Capping protein (CP) regulates actin polymerization by binding the barbed end of an actin filament, which blocks addition and loss of actin subunits. Recent structural and biochemical studies provide new insight into how cells control the actin capping activity of CP. Several molecules indirectly regulate CP by interacting with filament barbed ends and preventing binding of CP; others bind directly to CP and sterically block its interaction with an actin filament. A diverse and otherwise unrelated set of proteins contains a motif for CP regulation termed the “Capping Protein Interaction” (CPI) motif. These proteins bind directly to CP, recruit or target CP to a subcellular location, and modulate its actin-capping activity via allosteric effects.

The heterodimeric actin capping protein, referred to here as "CP," is an essential element of the actin cytoskeleton, binding to the barbed ends of actin filaments and regulating their polymerization. In vitro, CP has a critical role in the dendritic nucleation process of actin assembly mediated by Arp2/3 complex, and in vivo, CP is important for actin assembly and actin-based process of morphogenesis and differentiation. Recent studies have provided new insight into the mechanism of CP binding the barbed end, which raises new possibilities for the dynamics of CP and actin in cells. In addition, a number of molecules that bind and regulate CP have been discovered, suggesting new ideas for how CP may integrate into diverse processes of cell physiology.