Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics.     

Dynamic “Molecular Portraits” of Biomembranes Drawn by Their Lateral Nanoscale Inhomogeneities

To date, it has been reliably shown that the lipid bilayer/water interface can be thoroughly characterized by a sophisticated so-called “dynamic molecular portrait”. The latter reflects a combination of time-dependent surface distributions of various physicochemical properties, inherent in both model lipid bilayers and natural multi-component cell membranes. One of the most important features of biomembranes is their mosaicity, which is expressed in the constant presence of lateral inhomogeneities, the sizes and lifetimes of which vary in a wide range—from 1 to 10³ nm and from 0.1 ns to milliseconds. In addition to the relatively well-studied macroscopic domains (so-called “rafts”), the analysis of micro- and nanoclusters (or domains) that form an instantaneous picture of the distribution of structural, dynamic, hydrophobic, electrical, etc., properties at the membrane-water interface is attracting increasing interest. This is because such nanodomains (NDs) have been proven to be crucial for the proper membrane functioning in cells. Therefore, an understanding with atomistic details the phenomena associated with NDs is required. The present mini-review describes the recent results of experimental and in silico studies of spontaneously formed NDs in lipid membranes. The main attention is paid to the methods of ND detection, characterization of their spatiotemporal parameters, the elucidation of the molecular mechanisms of their formation. Biological role of NDs in cell membranes is briefly discussed. Understanding such effects creates the basis for rational design of new prospective drugs, therapeutic approaches, and artificial membrane materials with specified properties.     

5%Si高硅奥氏体不锈钢元素偏析及均匀化处理

 高硅奥氏体不锈钢由于高含量硅元素的加入使其具有优异的耐高温腐蚀性能和较低的成本,在制酸行业有着潜在的应用价值。然而,该合金中高含量硅元素的加入会促进凝固过程中溶质再分配,进而造成显著的元素偏析,最终导致合金内部产生枝晶组织和大量的有害相。对铸锭组织进行均匀化处理能够有效消除枝晶与元素偏析,促进析出相回溶和枝晶消融,从而改善材料的热塑性,有效应对热变形开裂问题。因此,采用金相显微镜(OM)、扫描电镜能谱分析(SEM/EDS)、电子探针(EPMA)、JMatPro软件计算等方法,研究了实验室条件下制备的5%Si高硅奥氏体不锈钢铸锭的显微组织和元素分布状态,通过残余偏析指数、扩散动力学计算并结合均匀化处理试验验证,最终确定了5%Si高硅奥氏体不锈钢合理的均匀化处理工艺。结果表明,5%Si高硅奥氏体不锈钢凝固过程中钼元素偏析最为严重,通过残余偏析指数模型计算得到的均匀化动力学方程可用来指导该成分合金的均匀化处理工艺;5%Si高硅奥氏体不锈钢经过1 150 ℃×12 h均匀化处理后,铸锭内枝晶消融,元素偏析基本消除,析出相与铁素体回溶到基体中,合金转变为全奥氏体组织,热塑性得到改善;当加热温度达到1 250 ℃时,合金出现过烧现象,晶界开始熔化。     

一种新的位错运动理论及对材料动态力学行为的描述

通过对位错在晶格内运动的动力学过程的全面分析。本文提出了一种考虑到粘性阻尼效应和热激活的位错集体运动统一理论。其特点是可用一简单的方程对从低速到高速运动的大量位错的平均行为进行统一描述。对ＫＣｌ晶体的典型实验怕拟合发现理论描述与实验结果相当一致。     

分子动力学在材料科学中的应用

分子动力学方法是进行物质原子或分子层次计算机模拟时所采用的一种基本方法。通过分子动力学模拟，可以给出原子尺度上材料及其演化过程细节的可能性，具有无先例的准确性，使材料设计和性能预测成为可能。本文分析了分子动力学模拟的基本原理和算法；综述了分子动力学在材料科学中的应用，介绍了最近发展的第一原理分子动力学模拟，指出材料科学中第一原理分子动力学模拟的应用还有待进一步发展。     

分子动力学模拟铜纳米团簇的结构稳定性

利用分子动力学研究了原子数为13～1 055的铜纳米团簇.结果表明:随着尺寸的减小,铜纳米团簇的结构发生晶体→非晶→晶体→非晶→晶体→非晶的转变.团簇平均原子结合能随着尺寸的减小而减小,且只依赖于短程有序,这说明了团簇平均原子结合能一般不能够作为非晶与密堆结构晶体转变的判据.平均原子间距不但依赖于团簇的尺寸,且对团簇结构的变化敏感,可以作为非晶与密堆结构晶体转变的一个判据.对偶分布函数的研究表明,大尺寸团簇的内部和表层原子结构都表现出晶格收缩效应,且不同于相应块体晶格,这表明了目前文献中关于团簇的块体加表面模型与壳核模型都有待改进.     

A modified embedded-atom method interatomic potential for the Fe–H system

A modified embedded-atom method (MEAM) interatomic potential for the Fe–H binary system has been developed using previously developed MEAM potentials of Fe and H. The potential parameters were determined by fitting to experimental data on the dilute heat of solution of hydrogen in body-centered cubic (bcc) and face-centered cubic (fcc) Fe, the vacancy–hydrogen binding energy in bcc Fe, and to a first-principles calculation for the lattice parameter and bulk modulus of a hypothetical NaCl-type FeH. The potential accurately reproduces the known physical properties of hydrogen as an interstitial solute element in bcc and fcc Fe. The applicability of the potential to atomistic approaches for investigating interactions between hydrogen atoms and other defects such as vacancies, dislocations and grain boundaries, and also for investigating the effects of hydrogen on various deformation and mechanical behaviors of iron is demonstrated.     

Simulation of nitrogen dynamics and biomass production in winter wheat using the Danish simulation model DAISY

A dynamic simulation model for the soil plant system is described. The model includes a number of main modules, viz., a hydrological model including a submodel for soil water dynamics, a soil temperature model, a soil nitrogen model including a submodel for soil organic matter dynamics, and a crop model including a submodel for nitrogen uptake. The soil part of the model has a one-dimensional vertical structure. The soil profile is divided into layers on the basis of physical and chemical soil characteristics. The simulation model was used to simulate soil nitrogen dynamics and biomass production in winter wheat grown at two locations at various levels of nitrogen fertilization. The simulated results were compared to experimental data including concentration of inorganic nitrogen in soil, crop yield, and nitrogen accumulated in the aboveground part of the crop. Based on this validation it is concluded that the overall performance of the model is satisfactory although some minor adjustments of the model may prove to be necessary.     

MD simulations of the collision between a copper ion and a polyethylene surface: an application to the plasma-insulating material interaction

To allow a better understanding of the physical phenomena occurred between a plasma and an insulating material, we have developed a specific MD code to study this type of interaction. We report results of MD simulations of the interaction of an incoming copper ion with a polyethylene crystal surface. Three initial incoming velocities and four impact angle values are used to check the influence of both the incident energy and impact direction to the resulting surface damage. When the incoming ion velocity is sufficiently high, MD results show that the impact can cause bond breaking leading to uncoordinated carbon atoms and free hydrogen atoms. The values of local temperatures associated with the structural changes show a possible ablation of the polyethylene surface.     

STUDY ON PERMEATION OF ACETONE/NITROGEN MIXED GAS THROUGH AL2O3 MICROPOROUS MEMBRANES: MOLECULAR DYNAMICS

In this work, by applying Materials Studio 2.2 software package, molecular dynamics (MD) was performed to investigate the dynamic processes of 1:4 acetone/nitrogen mixed gas permeating through different Al₂O₃ microporous membranes. Three systems were modeled by considering different box lengths, microporous sizes, and textures of Al₂O₃ membranes to compare different permeation behaviors. In each system, initial mixed gas contained 20 acetone molecules and 80 nitrogen molecules, and its density was set to 0.1 g/cm³. Analysis on the concentration profiles of nitrogen molecules (N2) and acetone molecules (Ace) in each system at different sampling times was implemented to discuss the permeation behaviors of smaller N2 and larger Ace. The results showed that adsorption and diffusion occurred synchronously but adsorption was dominant for acetone molecules and that the adsorption on the floor surface of the feed gas region more easily reached equilibrium (local equilibrium) than the diffusion and the adsorption on the ceiling of the initially vacuum region. Furthermore, for nitrogen, adsorption followed diffusion. Higher temperature is in favor of the enrichment of acetone on the floor surface of the feed gas region but against the adsorption of nitrogen. The adsorptive layer was found to be a double-layer with COMPASS force field and to be a monolayer with PCFF force field.