本文采用高性能的Discovery Studio 2021(DS2018R2)大分子计算模拟软件,在RCSB PDB数据库中调用蛋白质文件建立其立体结构,应用ZDOCK程序算法探究IL-18亚基(AB亚基或B亚基)与IL-18R相互作用的空间结构与构象变化,计算找到了相互作用界...本文采用高性能的Discovery Studio 2021(DS2018R2)大分子计算模拟软件,在RCSB PDB数据库中调用蛋白质文件建立其立体结构,应用ZDOCK程序算法探究IL-18亚基(AB亚基或B亚基)与IL-18R相互作用的空间结构与构象变化,计算找到了相互作用界面的氨基酸的一级序列与二级结构以及它们之间的相互作用力,并用拉氏图评估对接构象,研究发现B亚基在IL-18与IL-18R的结合中起主要作用。该计算方法与实验方法比较,可快速找到蛋白-蛋白相互作用的构象空间,优化膜蛋白相互作用的精度,其能从原子与量子水平探究细胞因子与膜蛋白受体的相互作用,其数据精确定量,有助于更深入解析分子机理。本文应用ZDOCK算法建立了通过计算模拟膜蛋白生物大分子相互作用的新领域,为细胞因子与化学因子的多肽类药物开发提供新的思路,为细菌病毒感染/肿瘤疾病的防治提供科学理论依据,在分子识别、神经元网络深度学习、生物信息处理领域具有广泛的应用。展开更多
黄曲霉毒素是一类化学结构类似的小分子化合物,均为二氢呋喃香豆素的衍生物,主要存在于土壤、动植物和各种坚果中,是霉菌毒素中毒性最大,对人类健康危害极为突出的一类霉菌毒素,而黄曲霉毒素的毒理机制始终不是很明确。计算机分子对接...黄曲霉毒素是一类化学结构类似的小分子化合物,均为二氢呋喃香豆素的衍生物,主要存在于土壤、动植物和各种坚果中,是霉菌毒素中毒性最大,对人类健康危害极为突出的一类霉菌毒素,而黄曲霉毒素的毒理机制始终不是很明确。计算机分子对接是模拟受体和底物之间通过能量匹配和几何匹配而相互识别的过程,其被广泛运用于虚拟筛选活性物质以及初步判断分子活性和毒性等领域,并对我们进行实体分子活性毒性试验起到了重要的指导作用。利用计算机分子对接软件Discovery Studio 3.1client,将6种常见黄曲霉毒素分子B1、B2、M1、M2、G1、G2与其具有强亲和性的蛋白进行虚拟对接实验,而这些蛋白在细胞凋亡、激素代谢、免疫抑制以及消化系统功能方面有重要的作用。通过本实验能够初步模拟黄曲霉毒素分子毒性作用位点,对于其毒理机制研究有重要的辅助作用。展开更多
计算机分子对接是模拟受体和底物之间通过能量匹配和几何匹配而相互识别的过程。其被广泛运用于虚拟筛选活性物质以及初步判断分子活性和毒性等领域,并对实体分子活性毒性实验起到了重要的指导作用。本实验是通过利用计算机分子对接软件...计算机分子对接是模拟受体和底物之间通过能量匹配和几何匹配而相互识别的过程。其被广泛运用于虚拟筛选活性物质以及初步判断分子活性和毒性等领域,并对实体分子活性毒性实验起到了重要的指导作用。本实验是通过利用计算机分子对接软件discovery studio 3.1client,以强雌激素活性的17β雌二醇作为阳性对照,对粮食中的主要毒性物质-玉米赤霉烯酮及其两种降解产物α-玉米赤霉醇、β-玉米赤霉醇的雌激素活性进行初步分析。实验结果表明,玉米赤霉烯酮、α-玉米赤霉醇、β-玉米赤霉醇对于雌激素的两种特异性受体α雌激素受体以及β雌激素受体的结合能量分别为-38.9894kcal/mol、-41.937kcal/mol、-27.6144kcal/mol,软件对接评分分别为:玉米赤霉烯酮113.570和106.956;α-玉米赤霉醇94.0647和72.6476;β-玉米赤霉醇115.28和107.458;计算机对接实验表明,这三种物质均有很强的雌激素活性,并且活性大小为:α-玉米赤霉醇>玉米赤霉烯酮>β-玉米赤霉醇。展开更多
For a complex flow about multi-element airfoils a mixed grid method is set up. C-type grids are produced on each element′s body and in their wakes at first, O-type grids are given in the outmost area, and H-type grid...For a complex flow about multi-element airfoils a mixed grid method is set up. C-type grids are produced on each element′s body and in their wakes at first, O-type grids are given in the outmost area, and H-type grids are used in middle additional areas. An algebra method is used to produce the initial grids in each area. And the girds are optimized by elliptical differential equation method. Then C-O-H zonal patched grids around multi-element airfoils are produced automatically and efficiently. A time accurate finite-volume integration method is used to solve the compressible laminar and turbulent Navier-Stokes (N-S) equations on the grids. Computational results prove the method to be effective.展开更多
With the aid of symbolic computation, we present the symmetry transformations of the (2+1)-dimensionalCaudrey-Dodd Gibbon-Kotera-Sawada equation with Lou's direct method that is based on Lax pairs. Moreover, witht...With the aid of symbolic computation, we present the symmetry transformations of the (2+1)-dimensionalCaudrey-Dodd Gibbon-Kotera-Sawada equation with Lou's direct method that is based on Lax pairs. Moreover, withthe symmetry transformations we obtain the Lie point symmetries of the CDGKS equation, and reduce the equation withthe obtained symmetries. As a result, three independent reductions are presented and some group-invariant solutions ofthe equation are given.展开更多
An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of n...An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski＇s rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA （topological polar surface area）, OH-NH interactions, n-violation and the molinspiration Log partition coefficient （miLogP） values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs （lpyy） and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher ＂FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski＇s rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.展开更多
Semantic Web Services is an emerging technology that promises to enable dynamic, execution-time discovery, composition, and invocation of Web Services. Semantic matchmaking plays a vital role in the automated and dyna...Semantic Web Services is an emerging technology that promises to enable dynamic, execution-time discovery, composition, and invocation of Web Services. Semantic matchmaking plays a vital role in the automated and dynamic discovery process of Semantic Web Services and consists in measuring the semantic distance between a requested service and an advertised one. In this paper, an innovative approach to effectively compute the semantic distance between Ontology Web Language for Services （OWL-S） annotated services is proposed. First, an edge-based method for measuring the semantic distance between Web Ontology Language （OWL） concepts is presented. Then, a comparison of the proposed measure and the one presented in a recent related work is made in order to show that our method is more efficient and fine-grained. Finally, some equations to compute semantic matchmaking of service capabilities, which are expressed in terms of inputs and outputs, are presented.展开更多
Objective Rheumatoid arthritis(RA)is an autoimmune disease involving the synovial lining of the major joints.Current therapies have noteworthy side effects.Our study involved in silico evaluation of Ehretia laevis(E.l...Objective Rheumatoid arthritis(RA)is an autoimmune disease involving the synovial lining of the major joints.Current therapies have noteworthy side effects.Our study involved in silico evaluation of Ehretia laevis(E.laevis)phytoconstituents targeting tumor necrosis factor-α(TNF-α).Methods Molecular docking studies performed to investigate the binding pattern of the plant E.laevis phytoconstituents along with the crystal structure of TNF-α(PDB ID:2 AZ5)using AutoDock Vina followed by a study of interacting amino acid residues and their influence on the inhibitory potentials of the active constituents.Further the pharmacokinetic profile and toxicity screening carried out using Swiss ADME and pk CSM.Results The docked results suggest that lupeol(-9.4 kcal/mol)andα-amyrin(-9.4 kcal/mol)has best affinity towards TNF-αcompared to standard drug thalidomide(-7.4 kcal/mol).The active chemical constituents represents better interaction with the conserved catalytic residues,leading to the inhibition/blockade of the TNF-α-associated signaling pathway in RA.Furthermore,pharmacokinetics and toxicity parameters of these phytochemicals were within acceptable limits according to ADMET studies.Conclusion The binding potential of phytoconstituents targeting TNF-αshowed promising results.Nonetheless,it encourages the traditional use of E.laevis and provides vital information on drug development and clinical treatment.展开更多
目的:利用对接方法对黄酮苷元类与表皮生长因子受体(epidermal growth factor receptor,EGFR)结合模式和能力进行研究,以阐明黄酮苷元类生物活性作用的理论基础。方法:从RCSB Protein Data Bank数据库检索受体表皮生长因子受体晶体结构...目的:利用对接方法对黄酮苷元类与表皮生长因子受体(epidermal growth factor receptor,EGFR)结合模式和能力进行研究,以阐明黄酮苷元类生物活性作用的理论基础。方法:从RCSB Protein Data Bank数据库检索受体表皮生长因子受体晶体结构,收集黄酮苷元类配体,用Schrodinger 8.0软件对受体和配体进行对接计算,分析受体和配体的作用模式和对接分数。结果:EGFR和黄酮苷元类配体能够较好对接,其作用模式大致分为Ⅰ、Ⅱ和Ⅲ3种,结合能力强的配体在活性结合位点可见氢键形成和亲脂基团,5、7位和4′位的取代对结合模式的影响较大。3、7、3′、4′位的取代的变化对结合能力影响较大。结论:黄酮苷元类化合物存在与EGFR较好的结合,其中可能有选择性和多靶标的EGFR抑制剂存在,其取代位置和方式可以影响结合模式和能力,对于研究黄酮苷元类抗肿瘤药物具有参考价值。展开更多
Contacts between two general blocks are the fundamental problem for discontinuous analysis. There are different contact points in different block positions, and there may have infinite contact point pairs in the same ...Contacts between two general blocks are the fundamental problem for discontinuous analysis. There are different contact points in different block positions, and there may have infinite contact point pairs in the same block position. In this paper, a new concept of an entrance block for solving the contacts between two general blocks is introduced. The boundary of an entrance block is a contact cover system. Contact covers may consist of contact vectors, edges, angles or polygons. Each contact cover defines a contact point and all closed-contact points define the movements, rotations and deformations of all blocks as in real cases. Given a reference point, the concept of entrance block simplifies the contact computation in the following ways.(1) The shortest distance between two blocks can be computed by the shortest distance between the reference point and the surface of the entrance block.(2) As the reference point outside the entrance block moves onto the surface of entrance block, the first entrance takes place. This first entrance point on the entrance block surface defines the contact points and related contact locations.(3) If the reference point is already inside the entrance block, it will exit the entrance block along the shortest path. The corresponding shortest exit point on the entrance block surface defines the contact points and related contact locations. All blocks and angles here are defined by inequality equations. Algebraic operations on blocks and angles are described here. Since the blocks and angles are point sets with infinite points, the geometric computations are difficult, and therefore the geometric computations are performed by related algebraic operations.展开更多
This paper constructs a new spectrum of networks by means of the matrix of link-state ofthe network,which can reveal the characteristics of the correlation between the degrees of the network.Also,the computation of th...This paper constructs a new spectrum of networks by means of the matrix of link-state ofthe network,which can reveal the characteristics of the correlation between the degrees of the network.Also,the computation of this spectrum of networks is usually more feasible and more efficient due tothe much lower order of its matrix of link-state than its adjacent matrix in practice.Some estimatesfor the bounds of the key eigenvalues in the spectrum are obtained,the corresponding inequalities arepresented and proved.For the sake of its application,the authors define spectrum of networks in twoways,and all theorems are given in parallel for both kinds of definition.In addition,the authors finda symmetry in the spectrum,which is relative to the characteristic of structure of its network to someextent.展开更多
文摘本文采用高性能的Discovery Studio 2021(DS2018R2)大分子计算模拟软件,在RCSB PDB数据库中调用蛋白质文件建立其立体结构,应用ZDOCK程序算法探究IL-18亚基(AB亚基或B亚基)与IL-18R相互作用的空间结构与构象变化,计算找到了相互作用界面的氨基酸的一级序列与二级结构以及它们之间的相互作用力,并用拉氏图评估对接构象,研究发现B亚基在IL-18与IL-18R的结合中起主要作用。该计算方法与实验方法比较,可快速找到蛋白-蛋白相互作用的构象空间,优化膜蛋白相互作用的精度,其能从原子与量子水平探究细胞因子与膜蛋白受体的相互作用,其数据精确定量,有助于更深入解析分子机理。本文应用ZDOCK算法建立了通过计算模拟膜蛋白生物大分子相互作用的新领域,为细胞因子与化学因子的多肽类药物开发提供新的思路,为细菌病毒感染/肿瘤疾病的防治提供科学理论依据,在分子识别、神经元网络深度学习、生物信息处理领域具有广泛的应用。
文摘黄曲霉毒素是一类化学结构类似的小分子化合物,均为二氢呋喃香豆素的衍生物,主要存在于土壤、动植物和各种坚果中,是霉菌毒素中毒性最大,对人类健康危害极为突出的一类霉菌毒素,而黄曲霉毒素的毒理机制始终不是很明确。计算机分子对接是模拟受体和底物之间通过能量匹配和几何匹配而相互识别的过程,其被广泛运用于虚拟筛选活性物质以及初步判断分子活性和毒性等领域,并对我们进行实体分子活性毒性试验起到了重要的指导作用。利用计算机分子对接软件Discovery Studio 3.1client,将6种常见黄曲霉毒素分子B1、B2、M1、M2、G1、G2与其具有强亲和性的蛋白进行虚拟对接实验,而这些蛋白在细胞凋亡、激素代谢、免疫抑制以及消化系统功能方面有重要的作用。通过本实验能够初步模拟黄曲霉毒素分子毒性作用位点,对于其毒理机制研究有重要的辅助作用。
文摘计算机分子对接是模拟受体和底物之间通过能量匹配和几何匹配而相互识别的过程。其被广泛运用于虚拟筛选活性物质以及初步判断分子活性和毒性等领域,并对实体分子活性毒性实验起到了重要的指导作用。本实验是通过利用计算机分子对接软件discovery studio 3.1client,以强雌激素活性的17β雌二醇作为阳性对照,对粮食中的主要毒性物质-玉米赤霉烯酮及其两种降解产物α-玉米赤霉醇、β-玉米赤霉醇的雌激素活性进行初步分析。实验结果表明,玉米赤霉烯酮、α-玉米赤霉醇、β-玉米赤霉醇对于雌激素的两种特异性受体α雌激素受体以及β雌激素受体的结合能量分别为-38.9894kcal/mol、-41.937kcal/mol、-27.6144kcal/mol,软件对接评分分别为:玉米赤霉烯酮113.570和106.956;α-玉米赤霉醇94.0647和72.6476;β-玉米赤霉醇115.28和107.458;计算机对接实验表明,这三种物质均有很强的雌激素活性,并且活性大小为:α-玉米赤霉醇>玉米赤霉烯酮>β-玉米赤霉醇。
文摘For a complex flow about multi-element airfoils a mixed grid method is set up. C-type grids are produced on each element′s body and in their wakes at first, O-type grids are given in the outmost area, and H-type grids are used in middle additional areas. An algebra method is used to produce the initial grids in each area. And the girds are optimized by elliptical differential equation method. Then C-O-H zonal patched grids around multi-element airfoils are produced automatically and efficiently. A time accurate finite-volume integration method is used to solve the compressible laminar and turbulent Navier-Stokes (N-S) equations on the grids. Computational results prove the method to be effective.
基金Supported by the Natural Key Basic Research Project of China under Grant No. 2004CB318000the 'Math + X' Key Project and Science Foundation of Dalian University of Technology under Grant No. SFDUT0808
文摘With the aid of symbolic computation, we present the symmetry transformations of the (2+1)-dimensionalCaudrey-Dodd Gibbon-Kotera-Sawada equation with Lou's direct method that is based on Lax pairs. Moreover, withthe symmetry transformations we obtain the Lie point symmetries of the CDGKS equation, and reduce the equation withthe obtained symmetries. As a result, three independent reductions are presented and some group-invariant solutions ofthe equation are given.
文摘An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski＇s rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA （topological polar surface area）, OH-NH interactions, n-violation and the molinspiration Log partition coefficient （miLogP） values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs （lpyy） and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher ＂FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski＇s rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.
文摘Semantic Web Services is an emerging technology that promises to enable dynamic, execution-time discovery, composition, and invocation of Web Services. Semantic matchmaking plays a vital role in the automated and dynamic discovery process of Semantic Web Services and consists in measuring the semantic distance between a requested service and an advertised one. In this paper, an innovative approach to effectively compute the semantic distance between Ontology Web Language for Services （OWL-S） annotated services is proposed. First, an edge-based method for measuring the semantic distance between Web Ontology Language （OWL） concepts is presented. Then, a comparison of the proposed measure and the one presented in a recent related work is made in order to show that our method is more efficient and fine-grained. Finally, some equations to compute semantic matchmaking of service capabilities, which are expressed in terms of inputs and outputs, are presented.
文摘Objective Rheumatoid arthritis(RA)is an autoimmune disease involving the synovial lining of the major joints.Current therapies have noteworthy side effects.Our study involved in silico evaluation of Ehretia laevis(E.laevis)phytoconstituents targeting tumor necrosis factor-α(TNF-α).Methods Molecular docking studies performed to investigate the binding pattern of the plant E.laevis phytoconstituents along with the crystal structure of TNF-α(PDB ID:2 AZ5)using AutoDock Vina followed by a study of interacting amino acid residues and their influence on the inhibitory potentials of the active constituents.Further the pharmacokinetic profile and toxicity screening carried out using Swiss ADME and pk CSM.Results The docked results suggest that lupeol(-9.4 kcal/mol)andα-amyrin(-9.4 kcal/mol)has best affinity towards TNF-αcompared to standard drug thalidomide(-7.4 kcal/mol).The active chemical constituents represents better interaction with the conserved catalytic residues,leading to the inhibition/blockade of the TNF-α-associated signaling pathway in RA.Furthermore,pharmacokinetics and toxicity parameters of these phytochemicals were within acceptable limits according to ADMET studies.Conclusion The binding potential of phytoconstituents targeting TNF-αshowed promising results.Nonetheless,it encourages the traditional use of E.laevis and provides vital information on drug development and clinical treatment.
文摘目的:利用对接方法对黄酮苷元类与表皮生长因子受体(epidermal growth factor receptor,EGFR)结合模式和能力进行研究,以阐明黄酮苷元类生物活性作用的理论基础。方法:从RCSB Protein Data Bank数据库检索受体表皮生长因子受体晶体结构,收集黄酮苷元类配体,用Schrodinger 8.0软件对受体和配体进行对接计算,分析受体和配体的作用模式和对接分数。结果:EGFR和黄酮苷元类配体能够较好对接,其作用模式大致分为Ⅰ、Ⅱ和Ⅲ3种,结合能力强的配体在活性结合位点可见氢键形成和亲脂基团,5、7位和4′位的取代对结合模式的影响较大。3、7、3′、4′位的取代的变化对结合能力影响较大。结论:黄酮苷元类化合物存在与EGFR较好的结合,其中可能有选择性和多靶标的EGFR抑制剂存在,其取代位置和方式可以影响结合模式和能力,对于研究黄酮苷元类抗肿瘤药物具有参考价值。
基金supported by the National Basic Research Program of China("973"Project)(Grant No.2014CB047100)
文摘Contacts between two general blocks are the fundamental problem for discontinuous analysis. There are different contact points in different block positions, and there may have infinite contact point pairs in the same block position. In this paper, a new concept of an entrance block for solving the contacts between two general blocks is introduced. The boundary of an entrance block is a contact cover system. Contact covers may consist of contact vectors, edges, angles or polygons. Each contact cover defines a contact point and all closed-contact points define the movements, rotations and deformations of all blocks as in real cases. Given a reference point, the concept of entrance block simplifies the contact computation in the following ways.(1) The shortest distance between two blocks can be computed by the shortest distance between the reference point and the surface of the entrance block.(2) As the reference point outside the entrance block moves onto the surface of entrance block, the first entrance takes place. This first entrance point on the entrance block surface defines the contact points and related contact locations.(3) If the reference point is already inside the entrance block, it will exit the entrance block along the shortest path. The corresponding shortest exit point on the entrance block surface defines the contact points and related contact locations. All blocks and angles here are defined by inequality equations. Algebraic operations on blocks and angles are described here. Since the blocks and angles are point sets with infinite points, the geometric computations are difficult, and therefore the geometric computations are performed by related algebraic operations.
基金supported by the Key Project for Fundamental Research of STCSM under Grant No. 06JC14057
文摘This paper constructs a new spectrum of networks by means of the matrix of link-state ofthe network,which can reveal the characteristics of the correlation between the degrees of the network.Also,the computation of this spectrum of networks is usually more feasible and more efficient due tothe much lower order of its matrix of link-state than its adjacent matrix in practice.Some estimatesfor the bounds of the key eigenvalues in the spectrum are obtained,the corresponding inequalities arepresented and proved.For the sake of its application,the authors define spectrum of networks in twoways,and all theorems are given in parallel for both kinds of definition.In addition,the authors finda symmetry in the spectrum,which is relative to the characteristic of structure of its network to someextent.
