HIV-1 Tat与P-TEFb复合物的分子动力学模拟及结合自由能计算

P-TEFb结构中与Tat蛋白的结合位点是新型抗HIV-1药物设计和虚拟筛选的重要靶标.对含有两个锌指结构的Tat.P-TEFb复合物体系进行了14ns的分子动力学模拟,应用MM-PBSA/GBSA方法计算体系的结合自由能,以及通过基于氨基酸残基的能量分解来探究体系中蛋白质之间的相互作用.结果表明范德华作用能是复合物形成的主要驱动力,Cys261与ZN88之间的配位作用是结合自由能的最大贡献者.根据Tat.P-TEFb体系的动力学结构信息和残基能量分解结果预测了P-TEFb结构中可能的活性位点.位点Ⅰ和位点Ⅱ应可作为基于受体三维结构的抗HIV-1药物分子设计的起始位点.模拟计算的结果可以为进一步指导药物设计奠定基础.     

多巴胺D3R蛋白同源模建及其应用

以分辨率为2.2的牛视紫红质蛋白的晶体结构为模板,采用同源模建方法,建立D3R模蛋白。对接D3R模蛋白与刺桐属配体分子,在对接的D3R蛋白的结合腔中选定一个以药物分子为质心,以半径为6的空间范围,计算此空间范围内的所有氨基酸残基与配体分子的作用能量,即残基/配体的结合能或排斥能,据此得到配体分子与受体蛋白的活性结合位点。     

自分泌运动因子(ATX)抑制剂结合位点的预测及其与rPAI-1的分子对接

利用复合物指纹的虚拟筛选预测自分泌运动因子(ATX)抑制剂的结合位点,并通过与24个抑制剂(10个脂质和脂基抑制剂,14个小分子抑制剂)分子对接和动力学模拟表明,Thr209,Asp172,Tyr306,Phe210,Leu243,Leu213和Phe274是抑制剂结合位点的重要残基,且这些残基均通过侧链与抑制剂作用.利用3D-partner预测出与ATX结合的蛋白为纤溶酶原激活物抑制剂1(rPAI-1),并通过同源模拟,得到rPAI-1的分子结构.利用软件GRAMM将ATX与rPAI-1分子结构相结合,并通过分子动力学模拟确定与大分子抑制剂rPAI-1作用的ATX重要残基Glu155和Ala158.     

三氢-咪唑并[4,5-c]喹啉-4(5H)-酮衍生物与二肽基肽酶-4结合机理的理论研究

通过分子对接、分子动力学(MD)模拟和结合自由能分析的方法研究了三氢-咪唑并[4,5-c]喹啉-4(5H)-酮衍生物药物与二肽基肽酶之间的成键机制,分析和讨论了抑制剂和相邻残基之间的氢键和疏水相互作用.用MM-PBSA方法计算得到的4个抑制剂的结合自由能与实验上测得的结果是一致的.抑制剂与DPP-4的关键残基间的范德华相互作用对于体系的结合能有较大的贡献,并且是区分不同抑制剂生物活性的标志之一.     

HIV-1 蛋白酶异位抑制剂体系的长时间分子动力学模拟

采用新开发的ff12SB力场在NVIDIA CUDA GPU上对HIV-1蛋白酶的活性位抑制剂体系和异位抑制剂体系分别进行了100 ns的长时间分子动力学模拟,并用MM-PB/GBSA方法计算了活性位点抑制剂TL-3与HIV-1蛋白酶的结合自由能。异位抑制剂体系中分子片段2-甲基环己醇结合在Exo位,有利于抑制剂被束缚在活性位点附近。异位抑制剂体系中抑制剂TL-3与蛋白酶的结合自由能为-85.78 kcal/mol,活性位抑制剂体系中为-79.45 kcal/mol。这些结果有助于深入了解HIV-1 PR的动力学过程,为设计新型强效抑制剂提供了新见解。     

乙酰胆碱酯酶AChE与其抑制剂1,3,4-噻二唑类衍生物的结合机理研究

阿尔茨海默病(Alzheimer’s disease,AD)是老年痴呆的一种,在老年人中有较高的发病率,乙酰胆碱酯酶抑制剂(AChEI)是目前广泛应用于临床治疗这类病症的主要药物.我们选择3种1,3,4-噻二唑抑制剂,分别与AChE进行分子对接和分子动力学(MD)模拟研究其结合模式以及相互作用机理.通过MM-PBSA方法分别计算了3种抑制剂与酶之间的自由结合能,计算结果与实验中测得的抑制剂的IC50值相一致.抑制剂与周围残基之间的氢键作用以及能量分析合理解释了AChE与抑制剂之间的结合模式以及相互作用机理.     

W301水分子在HIV-1蛋白酶和配体ABT-538结合中作用的QM/MM研究

结晶水分子W301在几乎所有的HIV-1蛋白酶（HIV-1PR）和配体的晶体结构中出现．在HIV-1PR中A链天门冬氨酸残基Asp25质子化状态或B链Asp25质子化状态下,QyaraM模拟后MM—GBSA方法计算得到W301水分子在HIV-1PR／ABT-538结合中的自由能贡献分别为-1．6．88kJ／mol、-17．63kJ／mol,W301水分子在HIV-1PR／ABT-538的结合中起到了关键的作用．进一步分析发现W301水分子与HIV-1PR和ABT-538分别形成了两个、四个氢键．     

分子动力学模拟三氯生对烯脂酰-ACP还原酶作用机制研究

本文利用分子动力学模拟分别研究了蛋白sa Fab I体系、sa Fab I-NADP+体系和sa Fab I-NADP+-TCL体系的稳定性、各氨基酸残基随模拟时间的波动情况以及活性位点处关键氨基酸残基构象的变化规律.研究表明,辅酶NADP+及抑制剂三氯生均可在不同程度上促使蛋白构象稳定.辅酶NADP+可以促使活性位点Loop区残基Y147-Y157残基构象变为规则的卷曲构象;抑制剂三氯生可以促使蛋白与底物结合位点Loop I区残基I94-E108和Loop II区残基R194-F204及活性位点Loop区残基Y147-Y157残基构象变为规则的卷曲构象,构象趋于稳定.上述研究发现对认识三氯生作为抗菌药物机制及相关药物设计具有重要指导意义.     

艾滋病毒蛋白酶异位抑制剂体系的分子动力学研究

对艾滋病毒蛋白酶异位抑制剂体系和活性位抑制剂体系进行8 ns的分子动力学模拟,用MM-PBSA方法分别计算了抑制剂与蛋白酶的结合自由能。异位抑制剂体系中抑制剂与蛋白酶的结合自由能为-90.30 kcal/mol,活性位抑制剂体系中为-59.58 kcal/mol。在异位抑制剂体系中分子片段4DX卡在蛋白酶的exo位,使蛋白酶活性位点附近残基的活动范围减小,有利于抑制剂被束缚在活性位点附近。异位抑制剂使体系刚性更强,更稳定,抑制剂与蛋白酶的结合更为牢固。     

HIV-1蛋白酶与抑制剂TMC-114作用机制的自由能研究

HIV-1蛋白酶已经成为治疗艾滋病的主要药物靶标之一.文中采用分子动力学模拟和MM-PBSA方法计算了HIV-1蛋白酶与TMC-114的结合自由能.通过能量分解考察了HIV蛋白酶的各残基与TMC-114的相互作用.     

An Index mechanism for multi-scale view in spatial databases

There are numerous geometric objects stored in the spatial databases. An importance function in a spatial database is that users can browse the geometric objects as a map efficiently. Thus the spatial database should display the geometric objects users concern about swiftly onto the display window. This process includes two operations:retrieve data from database and then draw them onto screen. Accordingly, to improve the efficiency, we should try to reduce time of both retrieving object and displaying them. The former can be achieved with the aid of spatial index such as R-tree, the latter require to simplify the objects. Simplification means that objects are shown with sufficient but not with unnecessary detail which depend on the scale of browse. So the major problem is how to retrieve data at different detail level efficiently. This paper introduces the implementation of a multi-scale index in the spatial database SISP (Spatial Information Shared Platform) which is generalized from R-tree. The difference between the generalization and the R-tree lies on two facets: One is that every node and geometric object in the generalization is assigned with a importance value which denote the importance of them, and every vertex in the objects are assigned with a importance value,too. The importance value can be use to decide which data should be retrieve from disk in a query. The other difference is that geometric objects in the generalization are divided into one or more sub-blocks, and vertexes are total ordered by their importance value. With the help of the generalized R-tree, one can easily retrieve data at different detail levels.Some experiments are performed on real-life data to evaluate the performance of solutions that separately use normal spatial index and multi-scale spatial index. The results show that the solution using multi-scale index in SISP is satisfying.     

Characterization of Ordovician carbonate reservoirs, southeastern Saskatchewan, Canada

The discovery of the prolific Ordovician Red River reservoirs in 1995 in southeastern Saskatchewan was the catalyst for extensive exploration activity which resulted in the discovery of more than 15 new Red River pools. The best yields of Red River production to date have been from dolomite reservoirs. Understanding the processes of dolomitization is, therefore, crucial for the prediction of the connectivity, spatial distribution and heterogeneity of dolomite reservoirs.The Red River reservoirs in the Midale area consist of 3～4 thin dolomitized zones, with a total thickness of about 20 m, which occur at the top of the Yeoman Formation. Two types of replacement dolomite were recognized in the Red River reservoir: dolomitized burrow infills and dolomitized host matrix. The spatial distribution of dolomite suggests that burrowing organisms played an important role in facilitating the fluid flow in the backfilled sediments. This resulted in penecontemporaneous dolomitization of burrow infills by normal seawater. The dolomite in the host matrix is interpreted as having occurred at shallow burial by evaporitic seawater during precipitation of Lake Almar anhydrite that immediately overlies the Yeoman Formation. However, the low δ18O values of dolomited burrow infills (-5.9‰～ -7.8‰, PDB) and matrix dolomites (-6.6‰～ -8.1‰, avg. -7.4‰ PDB) compared to the estimated values for the late Ordovician marine dolomite could be attributed to modification and alteration of dolomite at higher temperatures during deeper burial, which could also be responsible for its 87Sr/86Sr ratios (0.7084～0.7088) that are higher than suggested for the late Ordovician seawaters (0.7078～0.7080). The trace amounts of saddle dolomite cement in the Red River carbonates are probably related to "cannibalization" of earlier replacement dolomite during the chemical compaction.     

A computer generator for randomly layered structures

AcomputergeneratorforrandomlylayeredstructuresYUJia shun1,2,HEZhen hua2(1.TheInstituteofGeologicalandNuclearSciences,NewZealand;2.StateKeyLaboratoryofOilandGasReservoirGeologyandExploitation,ChengduUniversityofTechnology,China)Abstract:Analgorithmisintrod…     

Perspherical Approaches for Electrons in Atoms and Charged Excitons in Quantum Wells

Instead of following Fock’s expansion,we solve the Schrodinger equation for some quantum mechanical manybody systems such as electrons in atoms and charged excitons in quantum wells in a similar way in hyperspherical coordinates by expanding the wave functions into orthonormal complete basis sets of the hyperspherical hannonics(HHs)of hyperangles and generalized Laguerre polynomials(GLPs)of the hyperradius.This leads the equation to     

Advances in broadband wireless communications under high-mobility scenarios

Future mobile communication systems aim at providing very high data transmission rates, even in high-mobility scenarios such as high-speed wheel-track trains, maglev trains, highway vehicles, airplanes, guided missiles or spacecraft. A particularly important commercial application is the strong and increasing worldwide demand for high- speed broadband wireless communications （up to 574.8 km/ h test speeds or 380 km/h commercial speeds） in railways, providing data, voice and video services for applications such as onboard entertainment services to passengers, train control, train dispatch, train sensor status handling and sur- veillance. In such high-mobility scenarios, there are a number of communication challenges, including fast hand- over, location updating, high-speed channel modeling, estimation and equalization, anti-Doppler spreading tech- niques, fast power control, and dedicated network architec- ture. Because signal transmission in very high-speed scenarios will inevitably experience serious deterioration, it is imperative to develop key broadband mobile communi- cation techniques for such high-speed vehicles.     

Wuhan University Journal of Natural Sciences TOTAL CONTENTS

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Scale-based spatial data model for GIS

Being the primary media of geographical information and the elementary objects manipulated, almost all of maps adopt the layer-based model to represent geographic information in the existent GIS. However, it is difficult to extend the map represented in layer-based model. Furthermore, in Web-Based GIS, It is slow to transmit the spatial data for map viewing. In this paper, for solving the questions above, we have proposed a new method for representing the spatial data. That is scale-based model. In this model we represent maps in three levels: scale-view, block, and spatial object, and organize the maps in a set of map layers, named Scale-View, which associates some given scales.Lastly, a prototype Web-Based GIS using the proposed spatial data representation is described briefly.     

海南岛地体及其毗邻陆缘晚中生代—新生代古地磁研究和构造演化

本文叙述了对海南岛及其毗邻大陆边缘白垩纪到第四纪地层岩石进行古地磁研究的全部工作过程。通过分析岩石中剩余磁矢量的磁偏角及磁倾角的变化,提出海南岛白垩纪以来经历的构造演化模式如下:早期伴随顺时针旋转而向南迁移,后期伴随逆时针转动并向北运移。联系该地区及邻区的地质、地球物理资料,对海南岛上述的构造地体运动提出以下认识:北部湾内早期有一拉张作用,主要是该作用使湾内地壳显著伸长减薄,形成北部湾盆地。从而导致了海南岛的早期构造运动,而海南岛后期的构造运动则主要是受南海海底扩张的影响。海南地体运动规律的阐明对于了解北部湾油气盆地的形成演化有重要的理论和实际意义。     

Exciton Seebeck in Molecular Systems

Various applications relevant to the exciton dynamics,such as the organic solar cell,the large-area organic light-emitting diodes and the thermoelectricity,are operating under temperature gradient.The potential abnormal behavior of the exicton dynamics driven by the temperature difference may affect the efficiency and performance of the corresponding devices.In the above situations,the exciton dynamics under temperature difference is mixed with     

Achieving Unusual States of Matter Under High Pressure

The elongation method,originally proposed by Imamura was further developed for many years in our group.As a method towards O(N)with high efficiency and high accuracy for any dimensional systems.This treatment designed for one-dimensional(ID)polymers is now available for three-dimensional(3D)systems,but geometry optimization is now possible only for 1D-systems.As an approach toward post-Hartree-Fock,it was also extended to