The evolution of numerical methods for predicting the distribution of surfactant in the bubble-scale dynamics of foams

Many numerical methods now exist to simulate the structure and dynamics of surface-tension-dominated aqueous foams at the level of the individual films and the liquid structures where they meet. We review these methods, focusing in particular on bubble-scale simulations of foam rheology. We highlight methods that allow the distribution of surfactant during flow to be taken into account.     

Ultrafast Fluorescence Spectroscopy via Upconversion and Its Applications in Biophysics

In this review, the experimental set-up and functional characteristics of single-wavelength and broad-band femtosecond upconversion spectrophotofluorometers developed in our laboratory are described. We discuss applications of this technique to biophysical problems, such as ultrafast fluorescence quenching and solvation dynamics of tryptophan, peptides, proteins, reduced nicotinamide adenine dinucleotide (NADH), and nucleic acids. In the tryptophan dynamics field, especially for proteins, two types of solvation dynamics on different time scales have been well explored: ~1 ps for bulk water, and tens of picoseconds for “biological water”, a term that combines effects of water and macromolecule dynamics. In addition, some proteins also show quasi-static self-quenching (QSSQ) phenomena. Interestingly, in our more recent work, we also find that similar mixtures of quenching and solvation dynamics occur for the metabolic cofactor NADH. In this review, we add a brief overview of the emerging development of fluorescent RNA aptamers and their potential application to live cell imaging, while noting how ultrafast measurement may speed their optimization.     

Combined Experimental and Theoretical Insights into the Corrosion Inhibition Activity on Carbon Steel Iron of Phosphonic Acids

The inhibition effect of N,N′-phosphonomethylglycine (PMG) and vinyl phosphonic acid (VPA) on the 3% NaCl acidic solution corrosion of carbon steel iron was studied at different immersion times by potentiodynamic polarization, electrochemical impedance spectroscopy, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and computational methods. It is found from the polarization studies that PMG and VPA behave as mixed-type inhibitors in NaCl. Values of charge transfer resistance (R_ct) and double layer capacitance (C_dl) in the absence and presence of inhibitors are determined. The PMG and VPA inhibitors were capable of inhibiting the corrosion process up to ≈91% and ≈85%, respectively. In the presence of PMG, the synergic effect of chlorine ions was observed. Density functional theory (DFT) was engaged to establish the adsorption site of PMG, VPA, and their deprotonated states. For studied compounds, the resulted values of E_LUMO, E_HOMO, energy gap (∆E), dipole moment (μ), electronic hardness (η), global softness (σ), electrophilic index (ω), and the electronic potential map are in concordance with the experimental data results regarding their corrosion inhibition behavior and adsorption on the metal surface.     

Heterocyclic Substitutions Greatly Improve Affinity and Stability of Folic Acid towards FRα. an In Silico Insight

Folate receptor alpha (FRα) is known as a biological marker for many cancers due to its overexpression in cancerous epithelial tissue. The folic acid (FA) binding affinity to the FRα active site provides a basis for designing more specific targets for FRα. Heterocyclic rings have been shown to interact with many receptors and are important to the metabolism and biological processes within the body. Nineteen FA analogs with substitution with various heterocyclic rings were designed to have higher affinity toward FRα. Molecular docking was used to study the binding affinity of designed analogs compared to FA, methotrexate (MTX), and pemetrexed (PTX). Out of 19 FA analogs, analogs with a tetrazole ring (FOL03) and benzothiophene ring (FOL08) showed the most negative binding energy and were able to interact with ASP81 and SER174 through hydrogen bonds and hydrophobic interactions with amino acids of the active site. Hence, 100 ns molecular dynamics (MD) simulations were carried out for FOL03, FOL08 compared to FA, MTX, and PTX. The root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of FOL03 and FOL08 showed an apparent convergence similar to that of FA, and both of them entered the binding pocket (active site) from the pteridine part, while the glutamic part was stuck at the FRα pocket entrance during the MD simulations. Molecular mechanics Poisson-Boltzmann surface accessible (MM-PBSA) and H-bond analysis revealed that FOL03 and FOL08 created more negative free binding and electrostatic energy compared to FA and PTX, and both formed stronger H-bond interactions with ASP81 than FA with excellent H-bond profiles that led them to become bound tightly in the pocket. In addition, pocket volume calculations showed that the volumes of active site for FOL03 and FOL08 inside the FRα pocket were smaller than the FA–FRα system, indicating strong interactions between the protein active site residues with these new FA analogs compared to FA during the MD simulations.     

基于虚拟现实的分子对接教学软件*

由于其强大的沉浸性和交互性等特征,虚拟现实技术在教育教学方面有着独特的优势。基于分子建模工具和虚拟现实技术构建了一种关于分子对接的教学软件,该软件将语音讲解、动画演示、分子可视化、交互操作等内容有机整合在虚拟现实环境中,从理论知识讲解和VR实验操作2个方面展开,深入浅出地讲解了分子对接的知识点,达到辅助教学的目的。     

Inhibitor Development against p7 Channel in Hepatitis C Virus

Hepatitis C Virus (HCV) is the key cause of chronic and severe liver diseases. The recent direct-acting antiviral agents have shown the clinical success on HCV-related diseases, but the rapid HCV mutations of the virus highlight the sustaining necessity to develop new drugs. p7, the viroporin protein from HCV, has been sought after as a potential anti-HCV drug target. Several classes of compounds, such as amantadine and rimantadine have been testified for p7 inhibition. However, the efficacies of these compounds are not high. Here, we screened some novel p7 inhibitors with amantadine scaffold for the inhibitor development. The dissociation constant (Kd) of 42 ARD-series compounds were determined by nuclear magnetic resonance (NMR) titrations. The efficacies of the two best inhibitors, ARD87 and ARD112, were further confirmed using viral production assay. The binding mode analysis and binding stability for the strongest inhibitor were deciphered by molecular dynamics (MD) simulation. These ARD-series compounds together with 49 previously published compounds were further analyzed by molecular docking. Key pharmacophores were identified among the structure-similar compounds. Our studies suggest that different functional groups are highly correlated with the efficacy for inhibiting p7 of HCV, in which hydrophobic interactions are the dominant forces for the inhibition potency. Our findings provide guiding principles for designing higher affinity inhibitors of p7 as potential anti-HCV drug candidates.     

In silico virtual screening of potent inhibitor to hamper the interaction between HIV-1 integrase and LEDGF/p75 interaction using E-pharmacophore modeling,molecular docking,and dynamics simulations

The rapid increase of HIV-1 infection throughout the globe has a high demand for a superior drug with lesser side effects. LEDGF/p75, the human Lens Epithelium-Derived Growth Factor is identified as a promising cellular cofactor with integrase in facilitating the viral replication in an early stage by acting as a tethering factor in the pre-integration to the chromatin. Therefore, the present study was designed to identify a potent inhibitor by applying an E-pharmacophore based virtual screening, molecular docking, and dynamics simulation approaches. Finally, ZINC22077550 and ZINC32124441 were best identified potent molecules with the efficient binding affinity, strong hydrogen bonding, and acceptable pharmacological properties to hamper the interaction between integrase and LEDGF/p75. Further, the DFT and MDS studies were also analyzed, and shown a favorable energetic state and dynamic stability then reference compound. In conclusion, we suggest that these findings could be novel therapeutics in the future and may increase the lifespan of individuals suffering from viral infection.     

爆轰波对碰驱动平面锡飞层的动力学及动载行为特征研究

强冲击下的物质变形、破坏及诱发的轻重介质混合问题,是内爆压缩科学和工程应用领域的研究重点.本文针对爆轰波对碰条件下的复杂加载动力学过程及其动载破坏形态特征,开展数值模拟研究与极曲线理论分析.设计了爆轰波对碰驱动平面锡飞层的计算模型,获得了爆轰加载动力学过程及波系相互作用物理图像,分析了锡飞层对碰区自由表面速度历史的典型特征.给出了锡飞层中折射激波对碰发生马赫反射的临界条件,解读了三波结构的传播行为,阐明了对碰区内存在"一维正冲击"区域,一维区外存在单次斜冲击向两次斜冲击过渡的复杂加载动力学过程,提出了对碰区冲击动力学模型,揭示了影响对碰区动载行为特征的机理.数值模拟结果与极曲线理论分析结果相互印证,符合较好.本文的研究成果,将为深入理解和解读对碰区特殊的物质破坏及混合现象提供重要的理论支撑.     

基于临界电子密度的多载波微放电全局阈值分析

多载波微放电即发生在宽带、大功率真空无源微波部件中的二次电子倍增放电现象, 是影响空间和加速器应用中无源微波部件长期可靠性的主要隐患. 多载波微放电全局阈值功率的预测对于工作在真空环境中的微波部件至关重要, 但迄今尚无有效方法进行上述阈值的准确分析. 本文将微放电发生过程中二次电子分布区域等效为等离子体, 通过在理论上建立微波部件的电磁特性和电子密度间的对应关系, 提出了一种基于测试系统可检测水平的多载波微放电全局阈值功率分析方法. 为了能够通过蒙特卡罗优化方法得到全局阈值, 进一步基于电子加速的类半正弦等效, 提出了微放电演化过程中电子数涨落的快速计算方法. 基于以上两种方法得到的针对实际微波部件的全局阈值分析结果与实验结果相符合. 不同于传统基于多载波信号功率分析的经验方法, 本文基于临界电子密度判断依据和电子数涨落快速计算, 为多载波微放电全局阈值的准确预测提供了一种高效的分析方法.     

Mdm2生成速率调控的p53-Mdm2振子的全局动力学和稳定性

肿瘤抑制蛋白p53的动力学在一定程度上可以决定DNA损伤后的细胞命运.p53的动力学行为与p53信号通路中p53-Mdm2振子模块密切相关.然而,p53的负调控子Mdm2的生成速率的增加使其在一些癌细胞中过表达.因此探讨Mdm2生成速率对p53动力学的影响有重要意义.同时,PDCD5作为p53的激活子也调控p53的表达.因此,本文针对PDCD5调控的p53-Mdm2振子模型,通过分岔分析获得了Mdm2生成速率所调控的p53的单稳态、振荡以及单稳态与振荡共存的动力学行为,且稳定性通过能量面进行了分析.此外,噪声强度对p53动力学的稳定性有重要的影响.因此,针对p53的振荡行为,探讨了噪声强度对势垒高度和周期的影响.本文所获得的结果对理解DNA损伤后的p53信号通路调控起到一定的指导作用.