Inspired by biological systems that have the inherent skill to generate considerable bioelectricity from the salt content in fluids with highly selective ion channels and pumps on cell membranes, herein, a fully abiotic single‐pore nanofluidic energy‐harvesting system that efficiently converts Gibbs free energy in the form of a salinity gradient into electricity is demonstrated. The maximum power output with the individual nanopore approaches ∼26 pW. By exploiting parallelization, the estimated power density can be enhanced by one to three orders over previous ion‐exchange membranes. A theoretical description is proposed to explain the power generation with the salinity‐gradient‐driven nanofluidic system. Calculation results suggest that the electric‐power generation and its efficiency can be further optimized by enhancing the surface‐charge density (up to 100 mC m−2) and adopting the appropriate nanopore size (between 10 and 50 nm). This facile and cost‐efficient energy‐harvesting system has the potential to power biomedical tiny devices or construct future clean‐energy recovery plants.

The widespread use of tiny electrical devices, from microelectromechanical systems (MEMS) to portable personal electronics, provides a new challenge in the miniaturization and integration of power supply systems. Towards this goal, we have recently demonstrated a bio-inspired nanofluidic energy harvesting system that converts salinity gradient energy from the ambient environment into sustainable electricity with single ion-selective nanopores (Adv. Funct. Mater. 2010, 20, 1339. The nanofluidic reverse electrodialysis system (NREDS) significantly improves the performance of conventional membrane-based reverse electrodialysis systems due to a higher ionic flux and a lower fluidic resistance. However, the fundamental working mechanism of the NREDS has been largely unexplored in the literature. In this work we have systematically investigated the performance of the NREDS in relation to the electrolyte type and the charge selectivity of the nanofluidic channel using both experimental and theoretical approaches. Experimental results show that the short-circuit current, the open-circuit voltage, and the resulting electric power of the NREDS are very sensitive to the ionic composition of the electrolyte solution. Through an in-depth theoretical analysis, two dominant factors that govern the charge separation and ion selectivity of the nanochannels were identified. The results prove that, with well-matched electrolyte types and nanopore charge selectivity, the harvested electric power and energy conversion efficiency can be improved by nearly two orders of magnitude.

Parkinson's disease, originating from the intrinsically disordered peptide α-synuclein, is a common neurodegenerative disorder that affects more than 5% of the population above age 85. It remains unclear how α-synuclein monomers undergo conformational changes leading to aggregation and formation of fibrils characteristic for the disease. In the present study, we perform molecular dynamics simulations (over 180 μs in aggregated time) using a hybrid-resolution model, Proteins with Atomic details in Coarse-grained Environment (PACE), to characterize in atomic detail structural ensembles of wild type and mutant monomeric α-synuclein in aqueous solution. The simulations reproduce structural properties of α-synuclein characterized in experiments, such as secondary structure content, long-range contacts, chemical shifts, and (3)J(HNHCα )-coupling constants. Most notably, the simulations reveal that a short fragment encompassing region 38-53, adjacent to the non-amyloid-β component region, exhibits a high probability of forming a β-hairpin; this fragment, when isolated from the remainder of α-synuclein, fluctuates frequently into its β-hairpin conformation. Two disease-prone mutations, namely, A30P and A53T, significantly accelerate the formation of a β-hairpin in the stated fragment. We conclude that the formation of a β-hairpin in region 38-53 is a key event during α-synuclein aggregation. We predict further that the G47V mutation impedes the formation of a turn in the β-hairpin and slows down β-hairpin formation, thereby retarding α-synuclein aggregation.

DNA methylation is a key regulatory control route in epigenetics, involving gene silencing and chromosome inactivation. It has been recognized that methyl-CpG binding domain (MBD) proteins play an important role in interpreting the genetic information encoded by methylated DNA (mDNA). Although the function of MBD proteins has attracted considerable attention and is well characterized, the mechanism underlying mDNA recognition by MBD proteins is still poorly understood. In this article, we demonstrate that the methyl-CpG dinucleotides are recognized at the MBD–mDNA interface by two MBD arginines through an interplay of hydrogen bonding and cation-π interaction. Through molecular dynamics and quantum-chemistry calculations we investigate the methyl-cytosine recognition process and demonstrate that methylation enhances MBD–mDNA binding by increasing the hydrophobic interfacial area and by strengthening the interaction between mDNA and MBD proteins. Free-energy perturbation calculations also show that methylation yields favorable contribution to the binding free energy for MBD–mDNA complex.

Ring-shaped, hexameric ATPase motors fulfill key functions in cellular processes, such as genome replication, transcription or protein degradation, by translocating a long substrate through their central pore powered by ATP hydrolysis. Despite intense research efforts, the atomic-level mechanism transmitting chemical energy from hydrolysis into mechanical force that translocates the substrate is still unclear. Here we employ all-atom molecular dynamics simulations combined with advanced path sampling techniques and milestoning analysis to characterize how mRNA substrate is translocated by an exemplary homo-hexameric motor, the transcription termination factor Rho. We find that the release of hydrolysis product (ADP+Pi) triggers the force-generating process of Rho through a 0.1 millisecond-long conformational transition, the time scale seen also in experiment. The calculated free energy profiles and kinetics show that Rho unidirectionally translocates the single-stranded RNA substrate via a population shift of the conformational states of Rho; upon hydrolysis product release, the most favorable conformation shifts from the pre-translocation state to the post-translocation state. Via two previously unidentified intermediate states, the RNA chain is seen to be pulled by six K326 side chains, whose motions are induced by highly coordinated relative translation and rotation of Rho’s six subunits. The present study not only reveals in new detail the mechanism employed by ring-shaped ATPase motors, for example the use of loosely bound and tightly bound hydrolysis reactant and product states to coordinate motor action, but also provides an effective approach to identify allosteric sites of multimeric enzymes in general.