Cheng Yang

How PEGylation enhances the stability and potency of insulin: a molecular dynamics simulation.

While the effectiveness of PEGylation in enhancing the stability and potency of protein pharmaceuticals has been validated for years, the underlying mechanism remains poorly understood, particularly at the molecular level. A molecular dynamics simulation was developed using an annealing procedure that allowed an all-atom level examination of the interaction between PEG polymers of different chain lengths and a conjugated protein represented by insulin. It was shown that PEG became entangled around the protein surface through hydrophobic interaction and concurrently formed hydrogen bonds with the surrounding water molecules. In addition to enhancing its structural stability, as indicated by the root-mean-square difference (rmsd) and secondary structure analyses, conjugation increased the size of the protein drug while decreasing the solvent accessible surface area of the protein. All these thus led to prolonged circulation life despite kidney filtration, proteolysis, and immunogenic side effects, as experimentally demonstrated elsewhere. Moreover, the simulation results indicated that an optimal chain length exists that would maximize drug potency underpinned by the parameters mentioned above. The simulation provided molecular insight into the interaction between PEG and the conjugated protein at the all-atom level and offered a tool that would allow for the design of PEGylated protein pharmaceuticals for given applications.

Magnetic enzyme nanogel (MENG): a universal synthetic route for biocatalysts

A universal synthetic route for magnetic enzyme nanogels (MENGs) was proposed, based on electrostatic interaction driven assembly and in situ polymerization from the surface of magnetic nanoparticles, to avoid chemical modification of proteins and hence structural and functional deterioration.

Nanobiocatalysis in Organic Media: Opportunities for Enzymes in Nanostructures

In this review, we emphasized the importance of enzymatic processes in organic media, summarized recent advances of nanobiocatalysts with high activities in organic media, and proposed three general principles for designing nanobiocatalysis therein: facilitated substrate transport, retention of protein structure, and highly dispersed catalyst forms.

How hydrophobicity and the glycosylation site of glycans affect protein folding and stability: a molecular dynamics simulation.

Glycosylation is one of the most common post-translational modifications in the biosynthesis of protein, but its effect on the protein conformational transitions underpinning folding and stabilization is poorly understood. In this study, we present a coarse-grained off-lattice 46-β barrel model protein glycosylated by glycans with different hydrophobicity and glycosylation sites to examine the effect of glycans on protein folding and stabilization using a Langevin dynamics simulation, in which an H term was proposed as the index of the hydrophobicity of glycan. Compared with its native counterpart, introducing glycans of suitable hydrophobicity (0.1 < H < 0.4) at flexible peptide residues of this model protein not only facilitated folding of the protein but also increased its conformation stability significantly. On the contrary, when glycans were introduced at the restricted peptide residues of the protein, only those hydrophilic (H = 0) or very weak hydrophobic (H < 0.2) ones contributed slightly to protein stability but hindered protein folding due to increased free energy barriers. The glycosylated protein retained the two-step folding mechanism in terms of hydrophobic collapse and structural rearrangement. Glycan chains located in a suitable site with an appropriate hydrophobicity facilitated both collapse and rearrangement, whereas others, though accelerating collapse, hindered rearrangement. In addition to entropy effects, that is, narrowing the space of the conformations of the unfolded state, the presence of glycans with suitable hydrophobicity at suitable glycosylation site strengthened the folded state via hydrophobic interaction, that is, the enthalpy effect. The simulations have shown both the stabilization and the destabilization effects of glycosylation, as experimentally reported in the literature, and provided molecular insight into glycosylated proteins. The understanding of the effects of glycans with different hydrophobicities on the folding and stability of protein, as attempted by the present work, is helpful not only to explain the stabilization and destabilization effect of real glycoproteins but also to design protein-polymer conjugates for biotechnological purposes.

A Lipase‐Responsive Vehicle Using Amphipathic Polymer Synthesized with the Lipase as Catalyst

We describe an enzyme-responsive polymeric vehicle, which is of great interest in controlled drug delivery, biosensing, and other related areas. The polymer synthesized using lipase as catalyst in DMSO has a favorable molecular structure that is quickly hydrolyzed by lipase in aqueous phase, and allows a fast release of encapsulated molecules.

Green synthesis of enzyme/metal-organic framework composites with high stability in protein denaturing solvents

ObjectivesEnzyme/metal-organic framework composites with high stability in protein denaturing solvents were reported in this study.ResultsEncapsulation of enzyme in metal-organic frameworks (MOFs) via co-precipitation process was realized, and the generality of the synthesis was validated by using cytochrome c, horseradish peroxidase, and Candida antarctica lipase B as model enzymes. The stability of encapsulated enzyme was greatly increased after immobilization on MOFs. Remarkably, when exposed to protein denaturing solvents including dimethyl sulfoxide, dimethyl formamide, methanol, and ethanol, the enzyme/MOF composites still preserved almost 100% of activity. In contrast, free enzymes retained no more than 20% of their original activities at the same condition. This study shows the extraordinary protecting effect of MOF shell on increasing enzyme stability at extremely harsh conditions.ConclusionThe enzyme immobilized in MOF exhibited enhanced thermal stability and high tolerance towards protein denaturing organic solvents.

Directing lateral growth of lithium dendrites in micro-compartmented anode arrays for safe lithium metal batteries

Uncontrolled growth of lithium dendrites during cycling has remained a challenging issue for lithium metal batteries. Thus far, various approaches have been proposed to delay or suppress dendrite growth, yet little attention has been paid to the solutions that can make batteries keep working when lithium dendrites are already extensively present. Here we develop an industry-adoptable technology to laterally direct the growth of lithium dendrites, where all dendrites are retained inside the compartmented copper current collector in a given limited cycling capacity. This featured electrode layout renders superior cycling stability (e.g., smoothly running for over 150 cycles at 0.5u2009mAu2009cm−2). Numerical simulations indicate that reduced dendritic stress and damage to the separator are achieved when the battery is abusively running over the ceiling capacity to generate protrusions. This study may contribute to a deeper comprehension of metal dendrites and provide a significant step towards ultimate safe batteries.The formation of lithium dendrites remains a great challenge to lithium metal batteries. Here the authors show an anode design to laterally direct the dendrite growth inside the compartments, providing a feasible post-mortem solution to batteries with lithium dendrites already present.

Tuning defects in oxides at room temperature by lithium reduction

Defects can greatly influence the properties of oxide materials; however, facile defect engineering of oxides at room temperature remains challenging. The generation of defects in oxides is difficult to control by conventional chemical reduction methods that usually require high temperatures and are time consuming. Here, we develop a facile room-temperature lithium reduction strategy to implant defects into a series of oxide nanoparticles including titanium dioxide (TiO2), zinc oxide (ZnO), tin dioxide (SnO2), and cerium dioxide (CeO2). Our lithium reduction strategy shows advantages including all-room-temperature processing, controllability, time efficiency, versatility and scalability. As a potential application, the photocatalytic hydrogen evolution performance of defective TiO2 is examined. The hydrogen evolution rate increases up to 41.8u2009mmolu2009g−1u2009h−1 under one solar light irradiation, which is ~3 times higher than that of the pristine nanoparticles. The strategy of tuning defect oxides used in this work may be beneficial for many other related applications.Defective oxides are attractive for energy conversion and storage applications, but it remains challenging to implant defects in oxides under mild conditions. Here, the authors develop a versatile lithium reduction strategy to engineer the defects of oxides at roomxa0temperature leading to enhanced photocatalytic properties.

High performance, environmentally benign and integratable Zn//MnO2 microbatteries

With the explosive development of wearable electronics and the Internet of Things (IoT), it is highly desirable to develop miniaturized power sources with high performance, low-cost, environmental friendliness and integratable characteristics. Rechargeable microbatteries (MBs) can be used as the main power sources of future miniaturized wearable electronics, which have drawn broad attention recently. However, ever-reported MBs, such as micro-lithium batteries, have intrinsic safety hazards and environmental threats, and are not fully compatible with the green initiative of the IoT. Here, we report aqueous Zn//MnO2 MBs, with the merits of green, low cost and sustainability. By using a simple and scalable fabrication strategy, Zn//MnO2 MBs constructed with a three-dimensional (3D) MnO2@nickel nanocone array (NCA) cathode, a Zn@NCA anode, and a mild aqueous electrolyte containing ZnSO4 and MnSO4 can be prepared on a large scale. The as-prepared Zn//MnO2 MB reveals a superior capacity of 53.5 μA h cm−2 μm−1 at 1 C rate and a working voltage of 1.4 V. Moreover, it achieves a superior volumetric energy density of 71.3 μW h cm−2 μm−1, together with a peak power density of 1621.4 μW cm−2 μm−1, substantially higher than those of the reported lithium-ion MBs. Such an ultrathin (74 μm in thickness), lightweight (30 mg per unit) and flexible Zn//MnO2 MB component can power three pieces of LEDs. Last but not least, the fabrication strategy of our Zn//MnO2 MBs is fully compatible with flexible electronic fabrication processes. For instance, we have demonstrated that these Zn//MnO2 MBs could share the same fabrication process platform with radio frequency identification (RFID) tags. We envisage that our current technology would accelerate the use of miniaturized power sources for IoT applications, and inspire the development of intelligent manufacturing technology.

Lavender-like cobalt hydroxide nanoflakes deposited on nickel nanowire arrays for high-performance supercapacitors

Hierarchical nanostructured electrodes with excellent electronic properties and high specific surface areas have promising applications in high-performance supercapacitors. However, high active mass loading and uniform structure are still crucial in fabricating such architectures. Herein, Co(OH)2 nanoflakes were homogeneously deposited on nickel nanowire arrays (NNA) through a hydrothermal approach to form an NNA@Co(OH)2 (NNACOH) composite electrode. The as-synthesized one dimensional (1D) system had a lavender-like structure with a high mass loading of 5.42xa0mg cm−2 and a high specific surface area of 74.5 m2 g−1. Due to the unique electrode structure characteristics, the electrode could deliver a high specific capacitance of 891.2 F g−1 at the current density of 1 A g−1 (corresponding to an areal capacitance of 4.83 F cm−2 at 5.42 mA cm−2). The capacitance could still maintain a high value of 721 F g−1 when the current density is increased to 50 A g−1. In addition, the electrode showed superior cycle stability with a capacitance retention of 89.3% after charging/discharging at the current density of 10 A g−1 for 20u2006000 cycles. A flexible asymmetric supercapacitor (ASC) was assembled by employing NNACOH as the positive electrode and activated carbon (AC) as the negative electrode. It delivered a maximum energy density of 23.1 W h kg−1 at the power density of 712 W kg−1 and an energy density of 13.5 W h kg−1 at the maximum power density of 14.7 kW kg−1 (based on the total mass of the electrodes), showing the state-of-the-art energy storage ability of the Co(OH)2 cathode material at device level.