兔子朊蛋白结构稳定性的分子动力学研究(英文)

朊蛋白病是一种能够对人类和动物带来致命影响,并具有高度传染性的神经退行性疾病.兔子是目前已经报道的哺乳类动物中对朊蛋白病免疫的少数几个物种之一.我们将分子动力学和操控式分子动力学模拟相结合,研究了兔子正常朊蛋白的结构稳定性;同时讨论了蛋白结构的收敛性及刚性分布,并揭示了兔子朊蛋白中关键二级结构的动力学以及受力各向异性特征,证实了兔子朊蛋白结构的稳定性特征.     

麋鹿朊蛋白结构稳定性的分子动力学研究

朊蛋白病是一种致命且具有高度传染性的神经退行性疾病.糜鹿是目前已经报道的哺乳类动物中较易发生朊蛋白病的物种之一.作者使用分子动力学和操控式分子动力学模拟相结合的方法对糜鹿正常朊蛋白的结构稳定性进行了研究.发现了麋鹿朊蛋白结构中的不稳定结构域分布以及热动力学性质,揭示了糜鹿朊蛋白稳定性的分子结构基础以及力学特征.     

三种金属硫蛋白动力学稳定性的理论研究

对三类金属硫蛋白（大鼠金属硫蛋白亚型Ⅱ,兔肝金属硫蛋白亚型Ⅰ和兔肝金属硫蛋白亚型Ⅱ）的单体和二聚体进行了水溶液条件下的分子动力学模拟。其中大鼠金属硫蛋白亚型Ⅱ的结构直接来自于晶体数据,兔肝金属硫蛋白亚型Ⅰ和Ⅱ的结构则通过同源蛋白模型搭建。动力学模拟的结果显示,这三种单体在水溶液中都具有相当大的柔性,柔性主要来源于柔性区的氨基酸残基。三类金属硫蛋白单体的动力学模拟均表明α结构域的动力学稳定性都要优于     

多肽与朊蛋白相互作用研究

朊病毒病是一类累及多种动物和人类中枢神经系统退行性疾病,但至今针对这类疾病尚无有效的治疗方法.考虑到在180位的缬氨酸突变为异亮氨酸的180I突变蛋白的突变位点与朊蛋白181位的糖基化位点非常接近,其生物化学性质对朊病毒病的影响非常重要.本文针对180I突变蛋白的182-190段序列设计了KNFTK、KTDVE、EMMKE和EVVKK等四种αxyzβ型多肽.研究发现,四种多肽中只有EVVKK能稳定蛋白的构象,同时诱导β-折叠向α-螺旋的转变,而其他三种蛋白对180I的结构基本没有影响.该结论对于开发多肽药物并进一步用于临床治疗具有一定的借鉴作用.     

肝素诱导人细胞型朊蛋白构象变化的光谱表征

粘多糖在朊病毒病中所发挥的作用目前仍存在争议.以肝素钠作为粘多糖的代表,通过共振光散射光谱、荧光光谱和圆二色光谱的变化研究了肝素钠与人重组细胞型朊蛋白(rhPrPC23-231)的相互作用.结果表明,肝素钠与朊蛋白相互作用后光散射和荧光信号均得到增强,并且使朊蛋白的荧光寿命有一定程度的延长.圆二色光谱表明肝素钠能诱导朊蛋白从富含α-螺旋的构象向富含β-折叠的构象转变.     

谷朊蛋白的改性及应用

近20年来,利用动植物等可再生资源代替当前广泛使用的石化材料成为热门研究方向,是消除污染、保护环境、实现绿色化学、推进人类社会与环境和谐发展的唯一途径.谷朊蛋白是谷类淀粉加工的副产物,是植物代谢产生的天然植物蛋白,一种生物可降解、可再生的天然高分子.由于其独特的粘弹性、延伸性、薄膜成型性和热凝固性等,越来越受到人们的重视,不仅拓宽了在食品工业中的应用领域,还可作为价格适宜、性能优良的高分子材料应用于其它领域.本文介绍了有关谷朊蛋白的组成、近年来国内外改性原理和方法,及其潜在的应用.     

氢键对绿色荧光蛋白发色团类似物双光子吸收特性的影响（英文）

本文采用分子动力学模拟和量子化学计算相结合的方法,研究了氢键对一种新型供体-受体型绿色荧光蛋白发色团类似物的双光子吸收性质的影响.从分子动力学模拟中提取了氢键复合物的可能构型,并利用二次响应理论方法计算了发色团及其各种氢键复合物的双光子吸收性质,建立了氢键结构与双光子吸收性质之间的关系.结果表明,发色团与溶剂水分子可以通过O…H-O,N-H…O和N…H-O三种类型氢键相结合.O…H-O键的形成导致吸收波长发生红移,双光子吸收截面在一定程度上减小.N-H…O键可以在较长波长处显著增强双光子吸收,而N…H-O键会使吸收波长蓝移,并显著降低双光子吸收截面.应用两态模型,解释了氢键效应产生的原因,并绘制了相关分子轨道,分析了电荷转移特性.此外,通过统计各种氢键复合物的几率,获得了平均双光子吸收谱.本研究为利用氢键网络设计双光子吸收材料提供了良好的理论指导.     

电催化动力学简介（英文）

电催化过程是实现社会向可再生能源与化学品转型的主要驱动力之一。电催化动力学分析是探索反应机理和建立电催化剂构效关系行之有效的方法。本文将通过三个广泛研究的电催化反应：电化学CO₂、CO还原反应和氧还原反应,探讨Tafel分析的普遍过程、隐含假设以及需要注意的问题。此外,本文将介绍电化学反应活化参数的基本概念和关键热力学、动力学变量之间的关系。     

螺旋藻蛋白色素的稳定性研究

本文考察了螺旋藻蛋白色素（SP）的干粉和溶液的稳定性。SP干粉在暗处和室内自然光下较稳定，直射光下稍差。SP溶液在PH6～7时色泽呈蓝色，Cu2+对其稳定性有破坏作用，EDTA和柠檬酸可增强SP溶液稳定性，而明胶对其无影响，山梨酸对SP溶液色泽有良好的保护作用，SP在10％乙醇溶液或50％甘油溶液中较稳定。     

谷朊蛋白的改性及其作为纸张增强剂的性能

采用廉价可生物降解的小麦谷朊蛋白为原料,经过羟甲基化和阳离子化改性合成类似聚酰胺聚胺环氧氯丙烷(PPE)的纸张增强剂. 经改性后,谷朊蛋白带有氮杂环丁烷结构、表氯醇和环氧基团3种功能基团,可与纤维形成共价键,且能发生自身交联,在纤维周围形成三维交联网络结构,提高纸张干、湿强度. 通过单因素试验,研究了甲醛、甲酸、温度、反应时间和环氧氯丙烷5种反应因素对纸张强度的影响. 优化合成条件下制备改性谷朊蛋白可使纸张干抗张强度提高35%,湿强保留率达20%. 改性后谷朊蛋白显阳离子性,加入纸浆中,可使得浆料体系Zeta电位升高,改善浆料的留着率,明显提高纸张强度. 结果表明,经羟甲基化和环氧氯丙烷加成改性的谷朊蛋白可以作为纸张的干强剂和湿强剂.     

氯化钠对朊病毒结构稳定性影响的分子动力学研究

朊病毒疾病是由正常构象的PrPC转化为致病构象的PrPSc引起的一类可传染的蛋白质构象病.采用分子动力学模拟的方法研究了0～500mmol/L的NaCl溶液体系对人朊病毒构象影响并深入探讨了其分子机制.研究发现NaCl可以降低朊病毒的结构稳定性,并引起其α-螺旋含量的急剧降低.进一步的研究表明高浓度NaCl溶液体系能够显著破坏朊病毒螺旋1内部的重要盐桥Asp144-Arg148和Asp147-Arg151,同时明显降低其主要氢键Arg151 N:Asp147 O,Tyr150 N:Glu146 O,Tyr149 N:Tyr145 O和Arg148 N:Asp144 O的稳定性,并诱导朊病毒的疏水核心发生明显扩张,促使朊病毒整体稳定性的下降,这些可能是NaCl促进朊病毒构象转换的重要原因.     

Metadynamics simulation of prion protein: beta-structure stability and the early stages of misfolding

In the present study we have used molecular dynamics simulations to study the stability of the antiparallel beta-sheet in cellular mouse prion protein (PrP(C)) and in the D178N mutant. In particular, using the recently developed non-Markovian metadynamics method, we have evaluated the free energy as a function of a reaction coordinate related to the beta-sheet disruption/growth. We found that the antiparallel beta-sheet is significantly weaker in the pathogenic D178N mutant than in the wild-type PrP(C). The destabilization of PrP(C) beta-structure in the D178N mutant is correlated to the weakening of the hydrogen bonding network involving the mutated residue, Arg164 and Tyr128 side chains. This in turn indicates that such a network apparently provides a safety mechanism for the unzipping of the antiparallel beta-sheet in the PrP(C). We conclude that the antiparallel beta-sheet is likely to undergo disruption rather than growth under pathogenic conditions, in agreement with recent models of the misfolded monomer that assume a parallel beta-helix.     

A molecular dynamics study on the conformational stability of PrP 180–193 helix II prion fragment

Molecular dynamics of PrP 180–193 has allowed us to investigate the stability of the -helical conformation of the zwitterionic peptide (L₁) and the neutralized (L₂). In water, the helical structure of L₁ is unstable; in L₂, the -helix breaks up in the middle at Gln186, and the two resulting connected helices are stable. The hydrophobic enviroment decreases the stability of the helical structure of L₁, this effect is more evident for L₂ for which the unfolding of the C-terminus is followed by the formation of an intramolecular hydrogen bond connecting His¹⁸⁷ with Thr¹⁹¹.     

Palladium complexes affect the aggregation of human prion protein PrP106-126

Many neurodegenerative disorders are induced by protein conformational change. Prion diseases are characterized by protein conformational conversion from a normal cellular form (PrP(C)) to an abnormal scrapie isoform (PrP(Sc)). PrP106-126 is an accepted model for studying the characteristics of PrP(Sc) because they share many biological and physiochemical properties. To understand how metal complexes affect the property of the prion peptide, the present work investigated interactions between Pd complexes and PrP106-126 based on our previous research using Pt and Au complexes to target the peptide. The selected compounds (Pd(phen)Cl(2), Pd(bipy)Cl(2), and Pd(en)Cl(2)) showed strong binding affinity to PrP106-126 and affected the conformation and aggregation of this active peptide in a different binding mode. Our results indicate that it may be the metal ligand-induced spatial effect rather the binding affinity that contributes to better inhibition on peptide aggregation. This finding would prove valuable in helping design and develop novel metallodrugs against prion diseases.     

Metal-binding ability of human prion protein fragment peptides analyzed by column switch HPLC

The structural conversion of the prion protein (PrP) from the normal cellular isoform (PrP(C)) to the posttranslationally modified form (PrP(Sc)) is thought to relate to Cu2? binding to histidine (H) residues. Traditionally, the binding of metals to PrP has been investigated by monitoring the conformational conversion using circular dichroism (CD). In this study, the metal-binding ability of 21 synthetic peptides representing regions of human PrP(C) was investigated by column switch high-performance liquid chromatography (CS-HPLC). The CS-HPLC system is composed of a metal chelate affinity column and an octadecylsilica (ODS) reversed-phase column that together enable the identification of metal-binding regardless of conformational conversion. Synthetic peptides were designed with respect to the position of H residues as well as the secondary structure of human PrP (hPrP). The ability of the octapeptide (PHGGGWGQ)-repeating region (OP-repeat) to bind metals was analyzed by CS-HPLC and supported by CD analysis, and indicated that CS-HPLC is a reliable and useful method for measuring peptide metal-binding. Peptides from the middle region of hPrP showed a high affinity for Cu2?, but binding to Zn2?, Ni2?, and Co2? was dependent on peptide length. C-Terminal peptides had a lower affinity for Cu2?, Zn2?, Ni2?, and Co2? than OP-repeat region peptides. Interestingly, hPrP193-230, which contained no H residues, also bound to Cu2?, Zn2?, Ni2?, and Co2?, indicating that this region is a novel metal-binding site in the C-terminal region of PrP(C). The CS-HPLC method described in this study is useful and convenient for assessing metal-binding affinity and characterizing metal-binding peptides or proteins.