基于分子对接技术从虾夷扇贝中筛选抗SARS-CoV-2活性肽研究

为从食品原料中筛选具有抗2019新型冠状病毒(SARS-CoV-2)能力的生物活性肽段,选用虾夷扇贝肌球蛋白为目标序列,利用计算机对虾夷扇贝肌球蛋白进行模拟酶解,对酶解所得的肽段进行毒性和生物活性预测。选取活性评分超过0.5且无毒性的肽段,以SARS-CoV-S/ACE2复合蛋白和COVID-19 Mpro水解酶为靶标进行分子对接,鉴定其病毒抗性。结果表明:肽段CSNAIPEL可以与SARS-CoV-S/ACE2复合蛋白上的GLN42和GLU329两个关键氨基酸结合,LibDock Score为136.03;肽段LPIY不仅能与SARS-CoV-S/ACE2复合蛋白上的ASP38和TYR491氨基酸结合,还能够与COVID-19 Mpro上的THR24、THR25和THR26氨基酸结合,LibDock Score分别为142.85和168.04;肽段QRPR与COVID-19 Mpro水解酶晶体上的THR24、THR25和THR26氨基酸结合,LibDock Score为154.93。研究表明,肽段CSNAIPEL、LPIY和QRPR三者表现出较好的抗SARSCoV-2能力。本研究旨在为抗新型冠状病毒功能食品的研发提供新的思路。     

分子模拟在分子印迹技术中的应用研究

分子印迹技术应用到食品安全检测领域(农药与兽药残留检测),正成为国内外研究的热点,而分子模拟应用于分子印迹技术,可优化功能单体的筛选、分子识别机理的研究、印迹体系等几个方面。     

织物形象化仿真技术的进展

织物的形象化仿真是计算机图形学的研究热点内容之一，具有真实感的织物仿真枝术可以广泛应用于与人物角色相关的活动中。本文回顾了织物形象化仿真技术的研究概况，分析了现有的织物仿真模型的特点，并对织物形象化仿真技术的应用和发展进行了展望。     

大豆活性肽抗氧化力与其分子量关系的研究

大豆活性肽具有抗氧化性,其抗氧化力大小与大豆活性肽的分子量有关。采用凝胶柱层析分离法对碱性蛋白酶所制备的大豆活性肽(水解度为19.5%)进行分离纯化,得到六个组分,然后比较六个大豆活性肽组分(浓度均为1mg/mL)的抗氧化力大小,结果表明,组分4的抗氧化效果最好。用电喷雾质谱(ESI-MS)测定抗氧化大豆肽组分4的分子量,根据质谱图采用电喷雾质谱软件分析得出,抗氧化大豆肽组分4的平均分子量500,氨基酸数目为4个。     

小麦面筋蛋白功能短肽的阿片活性及其相对分子质量分布的研究

采用豚鼠回肠离体检定法对由不同蛋白酶(碱性蛋白酶、胰蛋白酶、胃酶、胰酶、中性蛋白酶和复合蛋白酶)水解制备的小麦面筋蛋白短肽的阿片活性进行了测定,结果表明,由碱性蛋白酶、胃酶、胃酶和胰酶复合水解制备的三种面筋蛋白短肽(AWGH、PWGH和PPWGH)具有较好的阿片活性,其IC50值分别为(1.21±0.25)、(1.29±0.38)、(1.57±0.21)mg/mL。采用高效液相色谱对AWGH、PWGH和PPWGH的相对分子质量分布研究发现,其相对分子质量在2000Da以下的组分占多数,并且AWGH中肽组分的分子量较PPWGH和PeWGH要更小一些。采用SephadexG-25对AWGH和PPWGH进行了初步分离,AWGH可以得到三个峰,而PPWGH可以得到五个峰。     

Prediction of peptides in the fermented cocoa storage protein,with reference to the modelled 3D structure

The amino acid sequence and a model for the three-dimensional (3D) structure of the cocoa storage protein have been combined with available data from protease digestions to aid understanding of factors that contribute to the characteristic cocoa aroma. Data reported for the free amino acids liberated during extensive digestions, modelling the fermentation process, are compared to computer predictions. Since good agreement is obtained between experiment and theory for the free amino acids, the modelling can be used to study properties not yet reported experimentally. In particular, the peptides that remain after digestion are predicted, highlighting those sequences which may play important roles in the production of cocoa aroma. This approach could prove equally useful in understanding other such systems. © 1998 SCI.     

两种血管紧张素转化酶抑制肽作用于靶标的分子机理

采用脱脂乳为原料,利用四步反相高压液相色谱从Lactobacillus helveticus 和Lactobacillus casei subsp. casei制作的酸乳中分离到两种血管紧张素转化酶Ⅰ(angiotensin Ⅰ -converting enzyme,ACE)抑制肽VPP 和IPP,测得它们抑制ACE 活性的IC50 分别为8.89μmol/L 和5.17μmol/L。根据氨基酸序列分析的结果,构建VPP 和IPP 的分子结构,通过分子柔性对接方法研究它们与ACE 相互作用的分子机理,确定它们的作用位点、作用力类型及相互作用能。结果表明：VPP、IPP 和ACE 的活性口袋之间均形成3 个氢键,且存在疏水,亲水等作用力,IPP 与ACE之间的结合较VPP 更稳定,与IPP 比VPP 具有较低的IC50 值的实验结果相一致。     

乳源ACE抑制肽作用于靶标模拟分子机理研究

利用分子柔性对接方法模拟研究4种较典型的血管紧张素转化酶Ⅰ(ACE)抑制肽KVLPVP(Lys-Val-Leu-Pro-Val-Pro)、YKVPQL(Tyr-Lys-Val-Pro-Gln-Leu)、VYPFPG(Val-Tyr-Pro-Phe-Pro-Gly)、IASGQP(Ile-Ala-Ser-Gly-Gln-Pro)与ACE相互作用的分子机理,确定它们的作用位点、作用力类型及相互作用能。结果表明：4种ACE抑制肽与ACE的活性口袋之间存在氢键、疏水、亲水、静电力、配位键等相互作用力,它们共同维持了肽与ACE复合物构象的稳定。ACE活性口袋中的关键氨基酸残基为：His353、Ala354、Ser355、Ala356、Glu384、Glu411、Pro519、Arg522、Tyr523,小肽分子中的关键基团为：氮端氨基、肽键羰基、碳端羧基;KVLPVP、YKVPQL、VYPFPG、IASGQP与ACE之间的结合能呈由低到高的趋势,表明它们与ACE之间的结合依次减弱,这与它们的IC50值依次增大的趋势相一致。     

Modelling consumer intakes of vegetable oils and fats

Vegetable oils and fats make up a significant part of the energy intake in typical European diets. However, their use as ingredients in a diverse range of different foods means that their consumption is often hidden, especially when oils and fats are used for cooking. As a result, there are no reliable estimates of the consumption of different vegetable oils and fats in the diet of European consumers for use in, for example, nutritional assessments or chemical risk assessments. We have developed an innovative model to estimate the consumption of vegetable oils and fats by European Union consumers using the European Union consumption databases and elements of probabilistic modelling. A key feature of the approach is the assessment of uncertainty in the modelling assumptions that can be used to build user confidence and to guide future development.     

Evolution of Moisture Distribution During Storage in a Composite Food Modelling and Simulation

In order to predict moisture transfer in a composite food, a mathematical model was developed and tested on a 2‐components system constituted of a sponge‐cake in contact with a fresh wet filling. Using independent sorption kinetic experiment, a power law was found as representative of the effect of moisture content on water effective diffusivity of sponge‐cake. The parameters of power law was then adjusted using the model optimization procedure on moisture profiles measurements of sponge‐cake in contact with a 0.99 water activity agar gel at 20°C. The model was validated with 0.95 and 0.90 water activity agar gels and successfully used to predict moisture transfer in a real food (processed cheese/sponge‐cake system).     

凝胶色谱测定核桃肽分子量方法比较

本文研究了核桃肽分子量的凝胶色谱色谱检测方法,对比两种测定肽类分子量大小常用的凝胶色谱柱:(1)国家标准GB/T22492-2008《大豆肽粉》以及GB/T 22729-2008《海洋鱼低聚肽粉》中推荐的TSK-GEL G2000 SWXL 7.8 mm×300 mm色谱柱;(2)商务部行业标准SB/T 10634-2011《淡水鱼胶原蛋白肽粉》中推荐的Superdex Peptide HR 10/30色谱柱。本文通过对四种单一标准品以及四种不同分子量大小的核桃肽样品在两种色谱条件中的结果对比分析,得出以下结论:TSK-GEL G2000 SWXL 7.8 mm×300 mm色谱柱推荐条件能在30 min内完成核桃肽的分离,检测线性良好,R2=0.97,色谱图峰形良好清晰,检测结果在10000 u以及1000 u区间上偏大;Superdex Peptide HR 10/30色谱柱推荐条件在80 min内完成核桃分离,检测线性较佳,R2=0.99,色谱图峰形出现裂峰与宽峰,检测结果在10000 u以及1000 u区间上偏小。     

大黄鱼蛋白源ACE抑制三肽的虚拟筛选、体外活性验证及分子机制

本文利用在线数据库对大黄鱼膜突蛋白虚拟酶解,对所得三肽的生物活性、亲水性、吸收、分布、代谢、排泄、毒性等性质进行预测,通过分子对接预测三肽与血管紧张素转化酶(angiotensin-1 converting enzyme,ACE)对接能量,同时对其体外ACE抑制活性测定,并阐明与ACE活性位点的分子作用机制.结果表明,...     

不同孵化时期鸡蛋蛋清小分子多肽的鉴定及功能分析

通过聚丙烯酰胺凝胶电泳(SDS-PAGE)和基质辅助激光解吸电离飞行时间串联质谱(MALDI-TOF MS/MS)技术,比较不同孵化时期鸡胚蛋蛋清中产生的小分子多肽,研究肽段与鸡胚发育之间的联系。结果显示在孵化第0、6、14、16 d分别得到837、879、872和842条肽段(共3430条)。除丛生蛋白肽段外,大部分被鉴定到的肽段来源于蛋清中低丰度蛋白。其中926条肽段来源于与鸡胚先天免疫有关的9种蛋白质,如防御素、白细胞介素6等;256条肽段来源于与鸡胚呼吸系统发育相关的3种蛋白质,cx9C基序蛋白、sprouty蛋白和碳酸酐酶。结果表明由蛋清蛋白质内源性酶降解形成的小分子多肽可能对鸡胚发育时形成的呼吸和免疫系统等发挥重要作用。     

肾素与抑制性地肤子皂苷相互作用的分子机制

地肤子中的木鳖子皂苷Ic和2’-O-β-D-吡喃葡萄糖木鳖子皂苷Ic有较强抑制肾素体外活性的功能。分子对接证实两皂苷与肾素结合较好,分别形成9 个和4 个氢键,氨基酸Ser230与Tyr231是氢键作用的关键残基,而Ala229、Met303、His301、Asp38、Arg82、Tyr83与Ile137则对疏水结合起重要作用。分子动力学模拟约1 000 ps后,两复合物平衡,均方根偏差分别为0.224 nm和0.219 nm,两皂苷降低了肾素链开始约160 个氨基酸的均方根波动。分子力学泊松-波尔兹曼表面积法获得的结合自由能分别为－44.36 kcal/mol与－62.46 kcal/mol,其中主要驱动力是静电和范德华作用,而极性溶剂化能则强烈阻碍结合。3 种方法综合揭示了两种地肤子皂苷抑制肾素的分子机制。     

基于生物信息学与分子对接技术对坛紫菜降血压肽的筛选及活性分析

采用木瓜蛋白酶和糜蛋白酶双酶联合水解坛紫菜蛋白（Porphyra haitanensis protein,PHP）制备降血压活性肽,测定了经超滤后各个分子质量PHP酶解液清除1,1-二苯基-2-三硝基苯肼（1,1-diphenyl-2-picrylhydrazyl,DPPH）自由基和2,2’-联氮双(3-乙基苯并噻唑啉-6-磺酸)（2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid),ABTS）阳离子自由基能力、铁离子还原抗氧化能力（ferric ion reducing antioxidant power,FRAP）以及血管紧张素转化酶（angiotensin converting enzyme,ACE）抑制活性。经质谱鉴定和活性肽数据库BIOPEP以及AHTPDB网站查找筛选活性肽,采用分子对接解释多肽抑制ACE机理,并对双酶酶解PHP动力学进行研究。结果表明：经超滤后的8?个分子质量的坛紫菜多肽组分中,＜0.5?kDa的组分具有最高DPPH自由基和ABTS阳离子自由基清除能力,＜1?kDa的组分具有最高FRAP值,而0.5～1?kDa组分IC50值（（2.21±0.28）mg/mL）最低。经查找筛选出14?条降血压肽,其中4?条肽的序列和对接能量分别为AVP（－5.87?kJ/mol）、GPL（－6.13?kJ/mol）、LDY（－7.65?kJ/mol）和LGYL（－7.78?kJ/mol）。酶解动力学模型预测PHP水解度与实验水解度相对误差在10%以下。本实验基于串联质谱与分子对接技术,通过生物信息筛选和体外活性检测从混合多肽中快速鉴定、筛选活性多肽,探究多肽抑制ACE的机理,并建立了描述蛋白可控酶解过程规律的动力学模型,为活性肽的制备提供了参考和借鉴。     

Molecular Dynamics Simulation for Mechanism Elucidation of Food Processing and Safety: State of the Art

Molecular dynamics (MD) simulation is a useful technique to study the interaction between molecules and how they are affected by various processes and processing conditions. This review summarizes the application of MD simulations in food processing and safety, with an emphasis on the effects that emerging nonthermal technologies (for example, high hydrostatic pressure, pulsed electric field) have on the molecular and structural characteristics of foods and biomaterials. The advances and potential projection of MD simulations in the science and engineering aspects of food materials are discussed and focused on research work conducted to study the effects of emerging technologies on food components. It is expected by showing key case studies that it will stir novel developments as a valuable tool to study the effects of emerging food technologies on biomaterials. This review is useful to food researchers and the food industry, as well as researchers and practitioners working on flavor and nutraceutical encapsulations, dietary carbohydrate product developments, modified starches, protein engineering, and other novel food applications.     

分子动力学模拟研究壳寡糖与脂肪酶相互作用机制

壳聚糖及其衍生物在酶固定化领域有着广泛的应用.了解酶与壳聚糖衍生物在分子水平上的相互作用机制,对相关生物催化剂的设计和应用具有重要意义.本研究采用分子动力学模拟方法研究南极假丝酵母脂肪酶B(CaLB)与壳寡糖(OCTS)的相互作用,并对脂肪酶与催化底物进行分子对接研究脂肪酶催化活性中心和底物结合构象和结合亲和力.结果表...     

利用同源建模、分子模拟和分子对接技术分析家蚕中碳酸酐酶的结构和催化机制

该研究以来源于家蚕的碳酸酐酶为研究对象,利用同源建模建立了家蚕碳酸酐酶的三维结构并预测了其潜在的活性区域。随后,利用Autodock-Vina对家蚕碳酸酐酶和底物进行分子对接,分析和评价了对接模型以及与乙酸对硝基苯酯底物对接过程中的相互作用。经分子动力学模拟和MM/PBSA,分析催化过程中家蚕碳酸酐酶的均方根偏差、溶剂可及面积以及径向分布函数。结果表明：建模所得的酶结构可靠性良好(完全允许区域为89.3%,允许区域10.3%,总和超过了99%);家蚕碳酸酐酶与底物的对接结合能为-6.1 Kcal/mol;范德华力在家蚕碳酸酐酶和底物的结合中占主导地位,而极性溶剂化对结合有显著的反作用;家蚕碳酸酐酶与底物的相互作用的区域为：138L～150V和209L～217C;同源建模所得的家蚕碳酸酐酶结构稳定(模拟最后50 ns RMSD值约0.35 nm)。该研究对后续进一步理性设计和改造家蚕碳酸酐酶提供了一定的理论支持。     

Molecular docking and dynamic insights on the adsorption effects of soy hull polysaccharides on bile acids

Molecular docking is a powerful tool that visualises interactions between receptors and ligands. This technique and experimental studies were used to explore the adsorption effects of soy hull polysaccharides (SHP) on bile acids (BAs). Docking sites and interactions between SHP and six BAs (deoxycholic acid, lycholic acid, taurine cholic acid, chenodeoxycholic acid, glycocholic acid and glycodesoxycholic acid) were identified by molecular docking. The docking sites were mainly O and H atoms, and interaction forces were mainly facilitated by hydrogen bonds and hydrophobic interactions, with hydrogen bonds being the main bond type. BAs-binding studies, Fourier-transform infrared spectroscopy and zeta potential results showed that hydrogen bonding was the main force mediating SHP and BAs adsorption. The hydrogen bonding was positively proportional to the adsorption capacity of BAs and negatively proportional to the absolute value of zeta potential. The molecular dynamic simulation of glycocholic acid and SHP was also performed. Hydrogen bond spacing and root mean square deviation analyses indicated that the glycocholic acid and SHP combination was stable. This study has the significance of preventing cardiovascular diseases by revealing the adsorption effects of SHP on bile acids BAs.