One touch is all it takes: the supramolecular interaction between ubiquitin and lanthanide complexes revisited by paramagnetic NMR and molecular dynamics.

The supramolecular interaction between lanthanide complexes and proteins is at the heart of numerous chemical and biological studies. Some of these complexes have demonstrated remarkable interaction properties with proteins or peptides in solution and in the crystalline state. Here we have used the paramagnetism of lanthanide ions to characterize the affinity of two lanthanide complexes for ubiquitin. As the interaction process is dynamic, the acquired NMR data only reflect the time average of the different steps. We have used molecular dynamics (MD) simulations to get a deeper insight into the detailed interaction scenario at the microsecond scale. This NMR/MD approach enabled us to establish that the tris-dipicolinate complex interacts specifically with arginines and lysines, while the crystallophore explores the protein surface through weak interactions with carboxylates. These observations shed new light on the dynamic interaction properties of these complexes, which will ultimately enable us to propose a crystallization mechanism.

Double-sides sticking mechanism of vinblastine interacting with α,ß-tubulin to get activity against cancer cells.

Vinblastine (VLB) and its derivatives have been used for clinical first-line drugs to treat various cancers. Due to the resistance and serious side effects from using VLB and its derivatives, there is a need to discover and develop novel VLB derivatives with high activity against cancer cells. In order to better discover and develop new VLB derivatives, we need to study the structural basis of VLB's anti-cancer cytotoxicity and the mechanism of its interaction with α,ß-tubulins. Based on the crystal structure of α,ß-microtubule complex protein, the molecular dynamics method including the sampling PMF method was used to study the variation of dissociation free energy (ΔG) of α,ß-tubulins under different system conditions, and then from which to study the mechanism of the interaction between VLB and α,ß-tubulins. The obtained results show that the dissociation of pure α,ß-tubulins requires 197.8 kJ·mol-1 for ΔG. When the VLB molecule exists between the interface of α,ß-tubulins, the dissociation ΔG of α,ß-tubulins reaches 220.5 kJ·mol-1, which is greater than that of pure α,ß-tubulin. The VLB molecule is formed by connecting a vindoline moiety (VM) molecule with a catharanthine moiety (CM) molecule through a carbon-carbon bond, which is a larger molecule. When the CM molecule exists in the middle of α,ß-tubulin interface, the dissociation ΔG of α,ß-tubulins is 46.2 kJ·mol-1, during which the CM moves with ß-tubulin. When the VM molecule exists between the middle of α,ß-tubulin interface, the dissociation ΔG of α,ß-tubulins is 86.7 kJ·mol-1, during which it moves with α-tubulin. Therefore, the VLB molecule is like a double-sides tape to stick α-tubulin and ß-tubulin together. The VLB molecule intervenes the dynamic equilibrium between dissociation and aggregation of α-tubulin and ß-tubulin by a double-sides sticking mechanism to exert high activity with toxicity against cancer cell. Besides, our results demonstrate that VLB has its structural basis for anticancer cytotoxicity due to its two compositions composed of a CM molecule and a VM molecule although they have little toxicity against cancer cell alone.

Adaptive backstepping-based tracking control design for nonlinear active suspension system with parameter uncertainties and safety constraints.

This paper proposes a novel constraint adaptive backstepping based tracking controller for nonlinear active suspension system with parameter uncertainties and safety constraints. By introducing the virtual control input and reference trajectories, the adaptive control law is developed to stabilize both of the vertical and pitch motions of vehicle body using backstepping technique and Lyapunov stability theory, and further to track the predefined reference trajectories within a finite time, which not only ensure the safety performance requirements, but also achieve improvements in riding comfort and handling stability of vehicle active suspension system. Next, the stability analysis on zero dynamics error system is conducted to ensure that all the safety performance indicators are all bounded and the corresponding upper bounds are estimable. Finally, a numerical simulation is provided to verify the effectiveness of the proposed controller and to address the comparability between the classical Barrier-Lyapunov Function based adaptive tracking controller and the proposed controller.

[X-ray fluorescence spectrum analysis of chemical element for spider and silkworm silk and its applications].

Elemental compositions in spider and silkworm silks were determined by X-ray fluorescence (XRF) spectrum to probe the silk-forming mechanisms and an elemental basis for spider silk with excellent characteristics. XRF analysis demonstrates that in the silkworm silk, the elemental content is 47.10% for C, 29.92% for O and 16. 52% for N, including metal elemental contents: 0.166 2% for Ca, 0.104 0% for Mg and 0.039 5% for K, while Na, Zn, Ni, Fe and Cr show less micro quantity. Due to relative high quantity for Ca and Mg, they both play an important role in the silk-forming mechanism by silkworm. In the spider silk, the determined main nonmetal elemental contents are 44.09% for C, 26.64% for O and 22.34% for N. The high content of nitrogen may be an elemental basis for spider silk with excellent characteristic. The main metal elemental contents are 0.268 0% for Na, 0.081 4% for K and 0.011 6% for Mg, while Ca, Zn, Ni, Cu and Cr possess less micro quantity in the spider silk. Because of relative high quantity for Na and K, they both play an important role in the silk-forming mechanism by spider. The elemental compositions investigated by using mathematic statistic method are quite in agreement with those demonstrated by using XRF spectrum, which validates the experimentally determined elemental compositions in the spider and silkworm silks.