新型抗爱滋病药物吡喃酮类化合物的三维定量构效关系研究

吡喃酮类化合物是抗爱滋病的一类新药。本文用ＣｏＭＦＡ方法对１９个吡喃酮类化合物的三维构效关系进行了研究。较详细地探讨了分子的重叠方式，并选用了其他有关的一些最优条件，得到满意的结果。     

Structural modeling and docking studies of ribose 5-phosphate isomerase from Leishmania major and Homo sapiens: A comparative analysis for Leishmaniasis treatment

Leishmaniases are caused by protozoa of the genus Leishmania and are considered the second-highest cause of death worldwide by parasitic infection. The drugs available for treatment in humans are becoming ineffective mainly due to parasite resistance; therefore, it is extremely important to develop a new chemotherapy against these parasites. A crucial aspect of drug design development is the identification and characterization of novel molecular targets. In this work, through an in silico comparative analysis between the genomes of Leishmania major and Homo sapiens, the enzyme ribose 5-phosphate isomerase (R5PI) was indicated as a promising molecular target. R5PI is an important enzyme that acts in the pentose phosphate pathway and catalyzes the interconversion of d-ribose-5-phosphate (R5P) and d-ribulose-5-phosphate (5RP). R5PI activity is found in two analogous groups of enzymes called RpiA (found in H. sapiens) and RpiB (found in L. major). Here, we present the first report of the three-dimensional (3D) structures and active sites of RpiB from L. major (LmRpiB) and RpiA from H. sapiens (HsRpiA). Three-dimensional models were constructed by applying a hybrid methodology that combines comparative and ab initio modeling techniques, and the active site was characterized based on docking studies of the substrates R5P (furanose and ring-opened forms) and 5RP. Our comparative analyses show that these proteins are structural analogs and that distinct residues participate in the interconversion of R5P and 5RP. We propose two distinct reaction mechanisms for the reversible isomerization of R5P to 5RP, which is catalyzed by LmRpiB and HsRpiA. We expect that the present results will be important in guiding future molecular modeling studies to develop new drugs that are specially designed to inhibit the parasitic form of the enzyme without significant effects on the human analog.     

A Hidden Markov Model applied to the protein 3D structure analysis

Understanding and predicting protein structures depend on the complexity and the accuracy of the models used to represent them. A Hidden Markov Model has been set up to optimally compress 3D conformation of proteins into a structural alphabet (SA), corresponding to a library of limited and representative SA-letters. Each SA-letter corresponds to a set of short local fragments of four C_α similar both in terms of geometry and in the way in which these fragments are concatenated in order to make a protein. The discretization of protein backbone local conformation as series of SA-letters results on a simplification of protein 3D coordinates into a unique 1D representation. Some evidence is presented that such approach can constitute a very relevant way to analyze protein architecture in particular for protein structure comparison or prediction.     

A survey of content based 3D shape retrieval methods

Recent developments in techniques for modeling, digitizing and visualizing 3D shapes has led to an explosion in the number of available 3D models on the Internet and in domain-specific databases. This has led to the development of 3D shape retrieval systems that, given a query object, retrieve similar 3D objects. For visualization, 3D shapes are often represented as a surface, in particular polygonal meshes, for example in VRML format. Often these models contain holes, intersecting polygons, are not manifold, and do not enclose a volume unambiguously. On the contrary, 3D volume models, such as solid models produced by CAD systems, or voxels models, enclose a volume properly. This paper surveys the literature on methods for content based 3D retrieval, taking into account the applicability to surface models as well as to volume models. The methods are evaluated with respect to several requirements of content based 3D shape retrieval, such as: (1) shape representation requirements, (2) properties of dissimilarity measures, (3) efficiency, (4) discrimination abilities, (5) ability to perform partial matching, (6) robustness, and (7) necessity of pose normalization. Finally, the advantages and limitations of the several approaches in content based 3D shape retrieval are discussed.

3D CAD model retrieval with perturbed Laplacian spectra

This paper presents a novel approach to the 3D CAD model retrieval, whereby the 3D models are treated and matched as undirected graphs. While there is much success made in the matching of graphs based on their spectral decomposition, most of these approaches consider smooth surfaces and are not suitable for CAD models because of their complex topology and singular structure. In the proposed approach, the models are simplified based on the piecewise flat properties of the surfaces first, and a perturbed Laplacian spectrum approach is then applied to characterize the shape. These spectral values are used as samples for spectral distribution estimation. The perturbed spectral distributions of different models are then compared by their KL-divergence for model retrieval. The proposed approach is tested with models from known 3D CAD database for verification.     

A language for representing and extracting 3D geometry semantics from paper-based sketches

Every product that exists, ranging from a toothbrush to a car, has first been conceived as a mental concept. Due to its efficacy in rapidly externalizing concepts, paper-based sketching is still extensively used by practising designers to gradually develop the three-dimensional (3D) geometric form of a concept. It is a common practice that form concepts are sketched on paper prior to generating 3D virtual models in commercial Computer-Aided Design (CAD) systems. However, the user-interface of such systems does not support automatic generation of 3D models from sketches. Furthermore, the inherent characteristics of form sketching (e.g. idiosyncrasy) pose a challenge to computer-based understanding of the form concept semantics expressed on paper. To address these issues, this paper is therefore concerned with the development of a visual language that is prescribed and to be used by product designers to annotate paper-based sketches such that the form geometry semantics can be formally represented; parsing the annotated sketch allows for the automatic generation of 3D virtual models in CAD. Inspired by re-usable 3D CAD modelling functions and the related environmental constraints and requirements, a prescribed sketching language, PSL, has been developed to annotate paper-based form sketches. The framework architecture which parses the annotated sketch and subsequently extracts the form concept semantics is described. Based on this framework, a prototype computer tool has been implemented and evaluated. Evaluation results provide a degree of evidence, first on the suitability of PSL in representing the semantics of a range of forms, and secondly on the designers׳ acceptance of taking up this annotated sketching approach in practice.     

3D QSAR comparative molecular field analysis on nonsteroidal farnesoid X receptor activators

Three-dimensional quantitative structure–activity relationships (3D QSAR) were performed for a series of farsenoid X receptor activators using comparative molecular field analysis (CoMFA). A training set containing 77 compounds served to establish the models. The best statistical results among all models were obtained with region focusing weighted by a S.D. × coefficient values of 0.8 and a grid spacing of 1.0 (r² = 0.963, SEE = 0.097; q² = 0.742, SEP = 0.255). The model was used to predict the potency of 20 test set compounds that were not included in the training set, and the predicted values were in good agreement with the experimental results. The final CoMFA model along with the information obtained from 3D contour maps should be useful for the design of novel FXR ligands having improved potency.     

光系统II抑制剂三维定量构效关系模型

光系统Ⅱ （ Ｐ ＳⅡ） 抑制剂通过抑制光合作用系统Ⅱ的电子传递使杂草因光合作用中断而死亡。本文选择不同骨架结构的 Ｐ ＳⅡ抑制剂, 由限定性构象搜索方法确定了重叠规则, 采用比较分子场分析方法进行了三维定量构效关系研究, 得出了具有较强预测能力的构效关系模型。     

The need for an integrated 2D/3D cad system in structural engineering

This paper identifies the engineering need for an integrated 2D/3D CAD system and outlines the features of a system that addresses this need. It is argued that an effective combination of 2D drafting and 3D modelling would allow many of the corresponding requirements to be met, particularly with respect to compliant drawings. It is postulated that the key to an effective combination of 2D and 3D is a unified data structure designed specifically for structural engineering applications. The concepts of a prototype data structure that could form the basis of such an integrated 2D/3D system are introduced and related to the engineering requirements.     

Extended Fitts' law for 3D pointing tasks using 3D target arrangements

This study explored an extended 3D Fitts' model, which was more appropriate than the original Fitts' model for pointing tasks in 3D environment. The inclination angle and azimuth angle for spherical coordinate system were added to Fitts' original model formulation. Experiments were conducted by manipulating the distance to the target, the size of target, and the 3D target arrangement, which were described using the two angles of inclination (θ1) and azimuth (θ2). Given the starting point as the center of the coordinates, θ1 was the angle between the positive y-axis and the target location, while θ2 was the angle between the positive x-axis and the projected target location on the x–z plane. All four variables were found to be significant for the movement time (MT) (p < 0.0001). After incorporating the two variables, θ1 and θ2, into the original Fitts' model, the extended Fitts' model with 3D target arrangements for spherical coordinate system showed better agreement with the empirical data than previous models in terms of the correlation coefficient and the standard error of the residuals for the measured and predicted MTs.Relevance to industryThis study presents an extended Fitts' model with a higher degree of predictability than previous studies for pointing task in three-dimensional space. In many situations, people implement pointing tasks in a three-dimensional environment, so it is important for designers to predict human performance accurately. Instead of using Euclidean coordinate system, spherical coordinate system can be also used for 3D pointing tasks. The extended model with spherical coordinate system can be used during the design and evaluation stage of the development process to help designers and developers.     

计算机辅助药物设计专家系统Apex中镇痛药物数据库的建立

文章扼要介绍了计算机辅助药物设计专家系统Ａｐｅｘ中镇痛药物建立的方法和过程，同时也讨论了用药物设计专家系统Ａｐｅｘ进行全新药物设计的方法，并依据哌替啶类药物的药效团设计了一个与这一药效团相符的新化合物。     

3D modelling of forest canopy structure for remote sensing simulations in the optical and microwave domains

A detailed 3D structural model of a conifer forest canopy was developed in order to simulate the reflectance (optical) and backscatter (microwave) signals measured remotely. We show it is feasible to model forest canopy scattering using detailed 3D models of tree structure including the location and orientation of individual needles. An existing structural growth model of Scots pine (Pinus sylvestris L.), Treegrow, was modified to simulate observed growth stages of a Scots pine canopy from age 5 to 50 years. The 3D tree models showed close structural agreement with in situ measurements. Needles were added to the structural models according to observed phyllotaxy (distribution). Individual trees were used to generate model canopies, which in turn were used to drive optical and microwave models of canopy scattering. Simulated canopy radiometric response was compared with airborne hyperspectral reflectance data (HyMAP) and airborne synthetic aperture RADAR (ASAR) backscatter data. Model simulations agreed well in general with observations, particularly at optical wavelengths where model simulations of low and high density canopy stands were shown to bracket observations. Relatively small sensitivity of observed reflectance to canopy age was captured reasonably well by the simulations. The choice of needle shape and phyllotaxy was shown to have a significant impact on multiple scattering behaviour at the branch scale. In the microwave domain, simulated backscatter values agreed reasonably well with observations at L-band, less so at X-band. L-band simulated backscatter significantly underestimated observed backscatter at younger canopy ages, probably as a result of inappropriate modelling of soil/understory. It is demonstrated that a combined structural and radiometric modelling approach provides a flexible and powerful method for simulating the remotely sensed signal of a forest canopy in the optical and microwave domains. This is particularly useful for exploring the impact of canopy structure on the resulting signal and also for combined retrievals of forest structural parameters from optical and microwave data.     

3D Image Synthesis for B-Reps Objects

This paper presents a new algorithm for generating 3D images of B-reps objects with trimmed surface boundaries.The 3D image is a discrete voxel-map representation within a Cubic Frame Buffer (CFB).The definition of 3D images for curve,surface and solid object are introduced which imply the connectivity and fidelity requirements.Adaptive Forward Differencing matrix (AFD-matrix) for 1D-3D manifolds in 3D space is developed.By setting rules to update the AFD-matrix,the forward difference direction and stepwise can be adjusted.Finally,an efficient algorithm is presented based on the AFD-matrix concept for converting the object in 3D space to 3D image in 3D discrete space.     

擦窗机悬挂轨道三维结构有限元分析

为探究某擦窗机悬挂结构的合理性,在AIP中创建其悬挂轨道的三维参数化特征模型,并根据轨道的结构、材料和特定工况受力等边界条件,建立悬挂系统的有限元模型,模拟计算2种有代表性的偏栽荷工况受力情况,得到悬挂轨道的三维应力分布、结构变形和安全因数．根据工程设计要求和初步分析结果,在保持边界条件和载荷条件不变的情况下,快速更新轨道结构参数,并通过比较分析确定塔楼悬挂轨道的最佳断面参数．该轨道及其固定间距、滑车滚轮和导向轮等构件均满足设计安全要求．     

非规则三维建筑模型的保结构变形

为了快速生成大量与输入风格一致的三维建筑模型,提出一种针对非规则三维建筑模型的保结构交互式变形技术.该技术以一般的三维网格模型作为输入,经过若干预处理操作形成带标记的包围盒层次结构,以此作为变形操作的分析基础.变形算法的核心思想是将原始的复杂结构分解为一组一维的结构序列,然后逐条对一维结构序列施加变形操作.在对一维结构序列的变形过程中尽可能以可重复的元素来填充变形空间,实现对输入结构特点的保持.实验结果表明,该技术可用于各种不同风格的建筑模型.     

ASM: An adaptive simplification method for 3D point-based models

Due to the popularity of computer games and computer-animated movies, 3D models are fast becoming an important element in multimedia applications. In addition to the conventional polygonal representation for these models, the direct adoption of the original scanned 3D point set for model representation is recently gaining more and more attention due to the possibility of bypassing the time consuming mesh construction stage, and various approaches have been proposed for directly processing point-based models. In particular, the design of a simplification approach which can be directly applied to 3D point-based models to reduce their size is important for applications such as 3D model transmission and archival. Given a point-based 3D model which is defined by a point set P () and a desired reduced number of output samples n^s, the simplification approach finds a point set P_s which (i) satisfies |P_s|=n^s (|P_s| being the cardinality of P_s) and (ii) minimizes the difference of the corresponding surface S_s (defined by P_s) and the original surface S (defined by P). Although a number of previous approaches has been proposed for simplification, most of them (i) do not focus on point-based 3D models, (ii) do not consider efficiency, quality and generality together and (iii) do not consider the distribution of the output samples. In this paper, we propose an Adaptive Simplification Method (ASM) which is an efficient technique for simplifying point-based complex 3D models. Specifically, the ASM consists of three parts: a hierarchical cluster tree structure, the specification of simplification criteria and an optimization process. The ASM achieves a low computation time by clustering the points locally based on the preservation of geometric characteristics. We analyze the performance of the ASM and show that it outperforms most of the current state-of-the-art methods in terms of efficiency, quality and generality.     

一种基于三维结构的分子相似性新定义

相似性模型在化学诸多领域的广泛应用激发了许多研究者努力探讨分子相似性更中肯的计算方法。我们根据语义模型定义了一种新的分子相似性指数。这种方法首先将分子结构安某种方式拆分，得到可以表征分子结构特征的结构碎片（子结构），它们构成了描述分子结构相似性的度量空间，再根据这些碎片的语义关系定义了分子相似。通过１６个含５个碳的醇之间的分子相似性的计算举例说明这个新方法。