Molecular Dynamics of CYFIP2 Protein and Its R87C Variant Related to Early Infantile Epileptic Encephalopathy

The CYFIP2 protein (cytoplasmic FMR1-interacting protein 2) is part of the WAVE regulatory complex (WRC). CYFIP2 was recently correlated to neurological disorders by the association of the R87C variant with early infantile epileptic encephalopathy (EIEE) patients. In this set of syndromes, the epileptic spasms and seizures since early childhood lead to impaired neurological development in children. Inside the WRC, the variant residue is at the CYFIP2 and WAVE1 protein interface. Thus, the hypothesis is that the R87C modification weakens this interaction, allowing the WRC complex’s constant activation. This work aimed to investigate the impacts of the mutation on the structure of the WRC complex through molecular dynamics simulation. For that, we constructed WRC models containing WAVE1-NCKAP1 proteins complexed with WT or R87C CYFIP2. Our simulations showed a flexibilization of the loop comprising residues 80–110 due to the loss of contacts between internal residues in the R87C CYFIP2 as well as the key role of residues R/C87, E624, and E689 in structural modification. These data could explain the mechanism by which the mutation impairs the stability and proper regulation of the WRC.     

Identification of Bacterial Membrane Selectivity of Romo1-Derived Antimicrobial Peptide AMPR-22 via Molecular Dynamics

The abuse or misuse of antibiotics has caused the emergence of extensively drug-resistant (XDR) bacteria, rendering most antibiotics ineffective and increasing the mortality rate of patients with bacteremia or sepsis. Antimicrobial peptides (AMPs) are proposed to overcome this problem; however, many AMPs have attenuated antimicrobial activities with hemolytic toxicity in blood. Recently, AMPR-11 and its optimized derivative, AMPR-22, were reported to be potential candidates for the treatment of sepsis with a broad spectrum of antimicrobial activity and low hemolytic toxicity. Here, we performed molecular dynamics (MD) simulations to clarify the mechanism of lower hemolytic toxicity and higher efficacy of AMPR-22 at an atomic level. We found four polar residues in AMPR-11 bound to a model mimicking the bacterial inner/outer membranes preferentially over eukaryotic plasma membrane. AMPR-22 whose polar residues were replaced by lysine showed a 2-fold enhanced binding affinity to the bacterial membrane by interacting with bacterial specific lipids (lipid A or cardiolipin) via hydrogen bonds. The MD simulations were confirmed experimentally in models that partially mimic bacteremia conditions in vitro and ex vivo. The present study demonstrates why AMPR-22 showed low hemolytic toxicity and this approach using an MD simulation would be helpful in the development of AMPs.     

Photorhabdus luminescens TccC3 Toxin Targets the Dynamic Population of F-Actin and Impairs Cell Cortex Integrity

Due to its essential role in cellular processes, actin is a common target for bacterial toxins. One such toxin, TccC3, is an effector domain of the ABC-toxin produced by entomopathogenic bacteria of Photorhabdus spp. Unlike other actin-targeting toxins, TccC3 uniquely ADP-ribosylates actin at Thr-148, resulting in the formation of actin aggregates and inhibition of phagocytosis. It has been shown that the fully modified F-actin is resistant to depolymerization by cofilin and gelsolin, but their effects on partially modified actin were not explored. We found that only F-actin unprotected by tropomyosin is the physiological TccC3 substrate. Yet, ADP-ribosylated G-actin can be produced upon cofilin-accelerated F-actin depolymerization, which was only mildly inhibited in partially modified actin. The affinity of TccC3-ADP-ribosylated G-actin for profilin and thymosin-β4 was weakened moderately but sufficiently to potentiate spontaneous polymerization in their presence. Interestingly, the Arp2/3-mediated nucleation was also potentiated by T148-ADP-ribosylation. Notably, even partially modified actin showed reduced bundling by plastins and α-actinin. In agreement with the role of these and other tandem calponin-homology domain actin organizers in the assembly of the cortical actin network, TccC3 induced intense membrane blebbing in cultured cells. Overall, our data suggest that TccC3 imposes a complex action on the cytoskeleton by affecting F-actin nucleation, recycling, and interaction with actin-binding proteins involved in the integration of actin filaments with each other and cellular elements.     

车轴径向锻造过程浅析

以某车轴径向锻造为例,分析锻造加热以及锻造工艺的特点,并且用滑移法分析径向锻造变形过程,建立了外摩擦影响下的滑移场模式,并做出了与之相对应的速端图。     

微波放电NO-O2-H2O-He体系脱除NO的数值模拟

采用微波放电NO-O2-H2O-He体系脱除NO的反应模型,对NO脱除及其转化进行分析计算。通过建立并数值求解化学反应动力学方程组,对NO-O2-H2O-He体系微波直接分解脱除NO过程进行反应动力学研究,分析影响NO脱除效率及其向N2和NO2转化的各种因素及规律。计算结果表明,在NO-O2-H2O-He体系中,微波功率,NO、O2和H2O的初始浓度等对NO脱除效率有较大影响,即微波功率的增大有利于NO的脱除及其向N2的转化;NO初始浓度的增加降低了体系的微波脱硝效率;脱硝效率随着模拟烟气相对湿度的增加而增加;微波放电条件下,O2的加入可增加产物中NO2的生成量;微波放电NO-O2-H2O-He体系脱除NO为还原和氧化反应共同作用的结果,NO转化为N2的效率总大于其转化为NO2的效率。     

加入CH4促进选择性非催化还原的CFD模拟研究

在实验研究和机理分析基础上利用计算流体动力学(computational fluid dynamics,CFD)软件Fluent,结合简化的反应机理模型,对沉降炉脱除NOx实验过程进行了模拟研究。模拟结果表明,在较低反应温度(1 073 K)下,喷入的氨基还原剂基本不与烟气中的NOx反应,形成较高的氨泄漏;而在较高的反应温度(1 373 K)下,喷入的氨基还原剂部分被烟气中的氧气氧化为NOx,导致NOx脱除效率较低。加入微量CH4能够促进较低温度下的选择性非催化还原(selective non-catalytic reduction,SNCR)反应,并减少氨泄露。在较高温度下SNCR反应速率加快,仍有部分NH3被氧化为NOx,但总体NOx脱除效率有所提高。模拟结果与实验结果的对比分析表明,采用简化的反应模型和CFD结合可以对常规SNCR反应和加入CH4的脱除NOx反应过程进行较为准确的模拟。     

Effects of vacancy structural defects on the thermal conductivity of silicon thin films

Vacancy structural defect effects on the lattice thermal conductivity of silicon thin films have been investigated with non-equilibrium molecular dynamics simulation.The lattice thermal conductivities decrease with increasing vacancy concentration at all temperatures from 300 to 700 K.Vacancy defects decrease the sample thermal conductivity,and the temperature dependence of thermal conductivity becomes less significant as the temperature increases.The molecular dynamics result is in good agreement with the theoretical analysis values obtained based on the Boltzmann equation.In addition,theoretical analysis indicates that the reduction in the lattice thermal conductivity with vacancy defects can be explained by the enhanced point-defect scattering due to lattice strain.     

钢板表面纵向裂纹的金相检验和分析

在连铸轧制的钢板表面有沿轧制方向的裂纹。采用化学成分分析,宏、微观检验等方法对裂纹进行了分析。结果表明,裂纹中存在氧化物及其脱碳等缺陷,这说明连铸坯表面在轧制前已存在裂纹并在轧前加热中裂纹内发生氧化和脱碳,导致轧制后的钢板表面出现裂纹。     

Effects of Tearing Conditions on the Crack Propagation in a Monolayer Graphene Sheet

The path of crack propagation in a graphene sheet is significant for graphene patterning via the tearing approach. In this study, we evaluate the fracture properties of pre-cracked graphene during the tearing process, with consideration of the effects of the aspect ratio, loading speed, loading direction, and ambient temperatures on the crack propagation in the monolayer sheet. Some remarkable conclusions are drawn based on the molecular dynamic simulation results, i.e., a higher loading speed may result in a complicated path of crack propagation, and the propagation of an armchair crack may be accompanied by sp carbon links at high temperatures. The reason for this is that the stronger thermal vibration reduces the load stress difference near the crack tip and, therefore, the crack tip can pass through the sp link. A crack propagates more easily along the zigzag direction than along the armchair direction. The out-of-plane tearing is more suitable than the in-plane tearing for graphene patterning. The path of crack propagation can be adjusted by changing the loading direction, e.g., a rectangular graphene ribbon can be produced by oblique tearing. This new understanding will benefit the application of graphene patterning via the tearing approach.     

Shape Transformations and Self-Assembly of Hairy Particles under Confinement

Molecular dynamics simulations are used to investigate the behavior of polymer-tethered nanoparticles between two inert or attractive walls. The confinement in pores creates new possibilities for controlling the shape transformation of individual hairy particles and their self-organization. We introduce a minimalistic model of the system; only chain-wall interactions are assumed to be attractive, while the others are softly repulsive. We show how the shape of isolated particles can be controlled by changing the wall separation and the strength of the interaction with the surfaces. For attractive walls, we found two types of structures, “bridges” and “mounds”. The first structures are similar to flanged spools in which the chains are connected with both walls and form bridges between them. We observed various bridges, symmetrical and asymmetrical spools, hourglasses, and pillars. The bridge-like structures can be “nano-oscillators” in which the cores jump from one wall to the other. We also study the self-assembly of a dense fluid of hairy particles in slit-like pores and analyze how the system morphology depends on interactions with the surfaces and the wall separation. The hairy particles form layers parallel to the walls. Different ordered structures, resembling two-dimensional crystalline lattices, are reported. We demonstrate that hairy particles are a versatile soft component forming a variety of structures in the slits.