Ionic Conductivity of β‐Cyclodextrin–Polyethylene‐Oxide/Alkali‐Metal‐Salt Complex

Highly conductive, crystalline, polymer electrolytes, β‐cyclodextrin (β‐CD)–polyethylene oxide (PEO)/LiAsF₆ and β‐CD–PEO/NaAsF₆, were prepared through supramolecular self‐assembly of PEO, β‐CD, and LiAsF₆/NaAsF₆. The assembled β‐CDs form nanochannels in which the PEO/X⁺ (X=Li, Na) complexes are confined. The nanochannels provide a pathway for directional motion of the alkali metal ions and, at the same time, separate the cations and the anions by size exclusion.     

Dynamics of water and sodium in gels under salt‐induced phase transition

Synthetic and biological gels undergo a sharp volume phase transition when subjected to a variety of environmental changes. Water and ion dynamics within swollen and compact phases are critical for understanding fundamental concepts in cellular (specifically neuronal) biophysics, for models of bound, free, or ordered water in complex environments; and for practical applications such as the design of gels for drug release, biomimetics, sensors, or actuators. In this work, we find, for the first time, basic physical parameters that shed light on the interaction of gels with water and electrolytes, across a volume phase transition. Water within a gel can be separated into bound and free populations with high exchange rate. We show that free water dynamics in compact gels are the same as those in pure water. Bound water was found to comprise a single layer around the polymers in both phases, with a correlation time three orders of magnitude higher than that of free water. Most importantly, salt‐induced phase transition was found to be different from a standard coil‐globule transition (e.g., temperature‐induced), with no rejection of bound water as the gel compacts. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 1620–1628     

Study of Endogen Substrates,Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics

Multidrug resistance protein-4 (MRP4) belongs to the ABC transporter superfamily and promotes the transport of xenobiotics including drugs. A non-synonymous single nucleotide polymorphisms (nsSNPs) in the ABCC4 gene can promote changes in the structure and function of MRP4. In this work, the interaction of certain endogen substrates, drug substrates, and inhibitors with wild type-MRP4 (WT-MRP4) and its variants G187W and Y556C were studied to determine differences in the intermolecular interactions and affinity related to SNPs using protein threading modeling, molecular docking, all-atom, coarse grained, and umbrella sampling molecular dynamics simulations (AA-MDS and CG-MDS, respectively). The results showed that the three MRP4 structures had significantly different conformations at given sites, leading to differences in the docking scores (DS) and binding sites of three different groups of molecules. Folic acid (FA) had the highest variation in DS on G187W concerning WT-MRP4. WT-MRP4, G187W, Y556C, and FA had different conformations through 25 ns AA-MD. Umbrella sampling simulations indicated that the Y556C-FA complex was the most stable one with or without ATP. In Y556C, the cyclic adenosine monophosphate (cAMP) and ceefourin-1 binding sites are located out of the entrance of the inner cavity, which suggests that both cAMP and ceefourin-1 may not be transported. The binding site for cAMP and ceefourin-1 is quite similar and the affinity (binding energy) of ceefourin-1 to WT-MRP4, G187W, and Y556C is greater than the affinity of cAMP, which may suggest that ceefourin-1 works as a competitive inhibitor. In conclusion, the nsSNPs G187W and Y556C lead to changes in protein conformation, which modifies the ligand binding site, DS, and binding energy.     

Point Mutations of Nicotinic Receptor α1 Subunit Reveal New Molecular Features of G153S Slow-Channel Myasthenia

Slow-channel congenital myasthenic syndromes (SCCMSs) are rare genetic diseases caused by mutations in muscle nicotinic acetylcholine receptor (nAChR) subunits. Most of the known SCCMS-associated mutations localize at the transmembrane region near the ion pore. Only two SCCMS point mutations are at the extracellular domains near the acetylcholine binding site, α1(G153S) being one of them. In this work, a combination of molecular dynamics, targeted mutagenesis, fluorescent Ca²⁺ imaging and patch-clamp electrophysiology has been applied to G153S mutant muscle nAChR to investigate the role of hydrogen bonds formed by Ser 153 with C-loop residues near the acetylcholine-binding site. Introduction of L199T mutation to the C-loop in the vicinity of Ser 153 changed hydrogen bonds distribution, decreased acetylcholine potency (EC₅₀ 2607 vs. 146 nM) of the double mutant and decay kinetics of acetylcholine-evoked cytoplasmic Ca²⁺ rise (τ 14.2 ± 0.3 vs. 34.0 ± 0.4 s). These results shed light on molecular mechanisms of nAChR activation-desensitization and on the involvement of such mechanisms in channelopathy genesis.     

Computational Analysis Reveals a Critical Point Mutation in the N-Terminal Region of the Signaling Lymphocytic Activation Molecule Responsible for the Cross-Species Infection with Canine Distemper Virus

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the n-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown, partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables the formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable the determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.     

Doxorubicin Encapsulation in Carbon Nanotubes Having Haeckelite or Stone–Wales Defects as Drug Carriers: A Molecular Dynamics Approach

Doxorubicin (DOX), a recognized anticancer drug, forms stable associations with carbon nanotubes (CNTs). CNTs when properly functionalized have the ability to anchor directly in cancerous tumors where the release of the drug occurs thanks to the tumor slightly acidic pH. Herein, we study the armchair and zigzag CNTs with Stone–Wales (SW) defects to rank their ability to encapsulate DOX by determining the DOX-CNT binding free energies using the MM/PBSA and MM/GBSA methods implemented in AMBER16. We investigate also the chiral CNTs with haeckelite defects. Each haeckelite defect consists of a pair of square and octagonal rings. The armchair and zigzag CNT with SW defects and chiral nanotubes with haeckelite defects predict DOX-CNT interactions that depend on the length of the nanotube, the number of present defects and nitrogen doping. Chiral nanotubes having two haeckelite defects reveal a clear dependence on the nitrogen content with DOX-CNT interaction forces decreasing in the order 0N > 4N > 8N. These results contribute to a further understanding of drug-nanotube interactions and to the design of new drug delivery systems based on CNTs.     

Redox- and protonation-state driven substrate-protein dynamics in respiratory complex I

Respiratory complex I is a key enzyme in the electron transport chains of mitochondria and bacteria. It transfers two electrons to quinone and couples this redox reaction to proton pumping to electrically charge the membrane it is embedded in. The charge and pH gradient across the membrane drives the synthesis of ATP. The redox reaction and proton pumping in complex I are separated in space and time, which raises the question of how the two reactions are coupled so efficiently. Here, we focus on the unique ～35 Å long tunnel of complex I, which houses the binding site of quinone reduction. We discuss the redox and protonation reactions that occur in this tunnel and how they influence the dynamics of protein and substrate. On the basis of recent structural data and results from molecular simulations, we review how quinone reduction and dynamics may be coupled to proton pumping in complex I.     

无序激光晶体及其超快激光研究进展

激光是受激辐射的光放大,所辐射的波长取决于增益介质中关键电子的能级结构,特别是其最外层电子的状态决定了可能实现的激光特性。激光发展60年来,激光晶体作为激光的重要激活材料,推动了激光技术的进步和普及,是一个研究历史长而又异常活跃的研究领域。当前,超短超强脉冲激光在加工、医疗、国防等关系国计民生的领域有重要需求,适合超短超强激光的激光晶体成为了本领域的研究热点,其关键是揭示最外层电子的影响因素及设计和生长具有宽波段发射性能的激光晶体。本论文从探讨影响激活离子光谱性能的关键因素出发,综述了以本课题组十余年研究的10余种无序激光晶体为主要部分的研究结果和进展,涉及晶体生长、晶体物理、激光器件设计及应用等工作,包含了高级、中级和低级对称性晶体及其获得的最短脉冲激光结果,希望能为本领域的后续研究提供一定的参考和借鉴。     

Dynamics modeling and robotic-assist,leader-follower control of tractor convoys

This paper proposes a generalized dynamics model and a leader-follower control architecture for skid-steered tracked vehicles towing polar sleds. The model couples existing formulations in the literature for the powertrain components with the vehicle-terrain interaction to capture the salient features of terrain trafficability and predict the vehicles response. This coupling is essential for making realistic predictions of the vehicles traversing capabilities due to the power-load relationship at the engine output. The objective of the model is to capture adequate fidelity of the powertrain and off-road vehicle dynamics while minimizing the computational cost for model based design of leader-follower control algorithms. The leader-follower control architecture presented proposes maintaining a flexible formation by using a look-ahead technique along with a way point following strategy. Results simulate one leader-follower tractor pair where the leader is forced to take an abrupt turn and experiences large oscillations of its drawbar arm indicating potential payload instability. However, the follower tractor maintains the flexible formation but keeps its payload stable. This highlights the robustness of the proposed approach where the follower vehicle can reject errors in human leader driving.     

Screening gas-phase chemical kinetic models: Collision limit compliance and ultrafast timescales

Detailed gas-phase chemical kinetic models are widely used in combustion research, and many new mechanisms for different fuels and reacting conditions are developed each year. Recent works have highlighted the need for error checking when preparing such models, but a useful community tool to perform such analysis is missing. In this work, we present a simple online tool to screen chemical kinetic mechanisms for bimolecular reactions exceeding collision limits. The tool is implemented on a user-friendly website, cloudflame.kaust.edu.sa, and checks three different classes of bimolecular reactions; (ie, pressure independent, pressure-dependent falloff, and pressure-dependent PLOG). In addition, two other online modules are provided to check thermodynamic properties and transport parameters to help kinetic model developers determine the sources of errors for reactions that are not collision limit compliant. Furthermore, issues related to unphysically fast timescales can remain an issue even if all bimolecular reactions are within collision limits. Therefore, we also present a procedure to screen ultrafast reaction timescales using computational singular perturbation. For demonstration purposes only, three versions of the rigorously developed AramcoMech are screened for collision limit compliance and ultrafast timescales, and recommendations are made for improving the models. Larger models for biodiesel surrogates, tetrahydropyran, and gasoline surrogates are also analyzed for exemplary purposes. Numerical simulations with updated kinetic parameters are presented to show improvements in wall-clock time when resolving ultrafast timescales.