The role of computer graphics and visualization in the GII

However captivating and encouraging its potential, the global information infrastructure (GII) has a long way to go before reaching full effectiveness. The GII must address real user needs and capabilities rather than developers' opinions on them. Otherwise, this information universe will become a cemetery, a massive burial site for an infinitely large amount of data and information. Visualization and computer graphics can play a central role in helping the GII meet its challenges. This report discusses how to use graphics and visualization technologies to do just that. We chose the topics for this report to represent some key challenges in interacting with structured and unstructured information distributed over the GII. The authors offer practical approaches to improving user interaction with the GII, especially the World Wide Web. Computer graphics and visualization provide effective tools for tackling the problems     

Insights into the induced fit mechanism in antithrombin-heparin interaction using molecular dynamics simulations

Heparin was isolated in the beginning of the 20th century and until today remains as one of the most important drugs able to interfere with the haemostatic process. Due to the side effects produced by heparin therapy, new promising drugs have been developed, as the synthetic pentasaccharide (synthetically derived from the sequence GlcN-GlcA-GlcN-IdoA-GlcN). The anticoagulant activity of this compound is based on potentiation of antithrombin (AT) inhibitory activity upon serine proteinases of clotting cascade, a mechanism based on the conformational modification of AT. In this context, we present here a molecular dynamics (MD) study of the interaction between the synthetic pentasaccharide and AT. The obtained data correctly predicted an induced fit mechanism in AT-pentasaccharide interaction, showing a solvent-exposed P1 residue instead of a hided conformation. Also, the specific contribution of important amino acid residues to the overall process was also characterized, both in (2)S(0) and (1)C(4) conformations of IdoA residue, suggesting that there is no conformational requirement to the interaction of this residue with AT. Altogether, the results show that MD simulations could be used to characterize and quantify the interaction of synthetic compounds with AT, predicting its specific capacity to induce conformational changes in AT structure. Thus, MD simulations of heparin (and heparin-derived)-AT interactions are proposed here as a powerful tool to assist and support drug design of new antithrombotic agents.     

Controlling the movement of crowds in computer graphics by using the mechanism of particle swarm optimization

This paper presents a uniform conceptual model to co-operate with particle swarm optimization (PSO) for controlling the movement of crowds in computer graphics. According to the PSO mechanism, each particle in the swarm adopts the information to automatically find a path from the initial position to the optimum. However, PSO aims to obtain the optimal solution instead of the searching path, while the purpose of this work concentrates on the control of the crowd movement, which is composed of the generated searching paths of particles. Hence, in order to generate seemingly natural, appropriate paths of people in a crowd, we propose a model to work with the computational facilities provided in PSO. Compared to related approaches previously presented in the literature, the proposed model is simple, uniform, and easy to implement. The results of the conducted simulations demonstrate that the coupling of PSO and the proposed technique can generate appropriate non-deterministic, non-colliding paths for the use in computer graphics for several different scenarios, including static and dynamic obstacles, moving targets, and multiple crowds.     

Recent developments in molecular graphics: visualization of chemical structures and properties

As three-dimensional models of chemical objects are essential tools for understanding their intimate structure and function, nowadays molecular graphics techniques allow building, visualizing, and manipulating, of complex molecular structures and their related properties. This paper presents several developments recently achieved in this field, namely: the representation of macromolecular structures such as proteins; the modelization of molecular envelopes as dot surfaces, mesh surfaces, and solid models; the evaluation and visualization of color-coded reactivity indices based on intermolecular interaction energies. The last application is shown to be particularly useful in several applications, such as molecular recognition and drug design.     

Petascale molecular dynamics simulation using the fast multipole method on K computer

In this paper, we report all-atom simulations of molecular crowding — a result from the full node simulation on the “K computer”, which is a 10-PFLOPS supercomputer in Japan. The capability of this machine enables us to perform simulation of crowded cellular environments, which are more realistic compared to conventional MD simulations where proteins are simulated in isolation. Living cells are “crowded” because macromolecules comprise ∼30% of their molecular weight. Recently, the effects of crowded cellular environments on protein stability have been revealed through in-cell NMR spectroscopy. To measure the performance of the “K computer”, we performed all-atom classical molecular dynamics simulations of two systems: target proteins in a solvent, and target proteins in an environment of molecular crowders that mimic the conditions of a living cell. Using the full system, we achieved 4.4 PFLOPS during a 520 million-atom simulation with cutoff of 28 Å. Furthermore, we discuss the performance and scaling of fast multipole methods for molecular dynamics simulations on the “K computer”, as well as comparisons with Ewald summation methods.     

Vectorization of molecular dynamics Fortran programs using the cyber 205 vector processing computer

A concept of vectorization of molecular dynamics Fortran programs for the use of the Cyber 205 machine is presented. It is shown that for calculations with larger particle systems the program runs faster on the 205 than on the Cray-1 by about a factor of two. Against conventional computers like the Cyber 175 an acceleration by a factor 10–15 is expected. A bit control vector is used instead of a neighbour list, which in principal provides calculations up to 6912 particles for the memory capacity of the Cyber 205. However, because the application of the bit vector requires computation times which grow proportional to N², the CPU time for particle numbers of more than 2048 becomes prohibitively large.     

Developments of multibody system dynamics: computer simulations and experiments

It is an exceptional success when multibody dynamics researchers Multibody System Dynamics journal one of the most highly ranked journals in the last 10 years. In the inaugural issue, Professor Schiehlen wrote an interesting article explaining the roots and perspectives of multibody system dynamics. Professor Shabana also wrote an interesting article to review developments in flexible multibody dynamics. The application possibilities of multibody system dynamics have grown wider and deeper, with many application examples being introduced with multibody techniques in the past 10 years. In this paper, the development of multibody dynamics is briefly reviewed and several applications of multibody dynamics are described according to the author’s research results. Simulation examples are compared to physical experiments, which show reasonableness and accuracy of the multibody formulation applied to real problems. Computer simulations using the absolute nodal coordinate formulation (ANCF) were also compared to physical experiments; therefore, the validity of ANCF for large-displacement and large-deformation problems was shown. Physical experiments for large deformation problems include beam, plate, chain, and strip. Other research topics currently being carried out in the author’s laboratory are also briefly explained. Commemorative Contribution.     

Insights into the folding pathway of the Engrailed Homeodomain protein using replica exchange molecular dynamics simulations

Protein folding studies were carried out by performing microsecond time scale simulations on the ultrafast/fast folding protein Engrailed Homeodomain (EnHD) from Drosophila melanogaster. It is a three-helix bundle protein consisting of 54 residues (PDB ID: 1ENH). The positions of the helices are 8-20 (Helix I), 26-36 (Helix II) and 40-53 (Helix III). The second and third helices together form a Helix-Turn-Helix (HTH) motif which belongs to the family of DNA binding proteins. The molecular dynamics (MD) simulations were performed using replica exchange molecular dynamics (REMD). REMD is a method that involves simulating a protein at different temperatures and performing exchanges at regular time intervals. These exchanges were accepted or rejected based on the Metropolis criterion. REMD was performed using the AMBER FF03 force field with the generalised Born solvation model for the temperature range 286-373 K involving 30 replicas. The extended conformation of the protein was used as the starting structure. A simulation of 600 ns per replica was performed resulting in an overall simulation time of 18 μs. The protein was seen to fold close to the native state with backbone root mean square deviation (RMSD) of 3.16 ?. In this low RMSD structure, the Helix I was partially formed with a backbone RMSD of 3.37 ? while HTH motif had an RMSD of 1.81 ?. Analysis suggests that EnHD folds to its native structure via an intermediate in which the HTH motif is formed. The secondary structure development occurs first followed by tertiary packing. The results were in good agreement with the experimental findings.     

Material and geometric nonlinear dynamic analysis of steel frames using computer graphics

A promising analytical model for nonlinear dynamic analysis of steel frames is described. This approach is based on an updated Lagrangian formulation in conjunction with force-space, concentrated plasticity. Kinematic strain hardening behavior is modelled by the bounding-surface concept. The analysis is implemented in a highly interactive, adaptive fashion using computer graphics and a super-minicomputer. Several examples illustrate the effectiveness of the analysis strategy described.     

Phase-transfer energetics of small-molecule alcohols across the water-hexane interface: molecular dynamics simulations using charge equilibration models

We study the water-hexane interface using molecular dynamics (MD) and polarizable charge equilibration (CHEQ) force fields. Bulk densities for TIP4P-FQ water and hexane, 1.0086±0.0002 and 0.6378±0.0001 g/cm(3), demonstrate excellent agreement with experiment. Interfacial width and interfacial tension are consistent with previously reported values. The in-plane component of the dielectric permittivity (?(||)) for water is shown to decrease from 81.7±0.04 to unity, transitioning longitudinally from bulk water to bulk hexane. ?(||) for hexane reaches a maximum in the interface, but this term represents only a small contribution to the total dielectric constant (as expected for a non-polar species). Structurally, net orientations of the molecules arise in the interfacial region such that hexane lies slightly parallel to the interface and water reorients to maximize hydrogen bonding. Interfacial potentials due to contributions of the water and hexane are calculated to be -567.9±0.13 and 198.7±0.01 mV, respectively, giving rise to a total potential in agreement with the range of values reported from previous simulations of similar systems. Potentials of mean force (PMF) calculated for methanol, ethanol, and 1-propanol for the transfer from water to hexane indicate an interfacial free energy minimum, corresponding to the amphiphilic nature of the molecules. The magnitudes of transfer free energies were further characterized from the solvation free energies of alcohols in water and hexane using thermodynamic integration. This analysis shows that solvation free energies for alcohols in hexane are 0.2-0.3 kcal/mol too unfavorable, whereas solvation of alcohols in water is approximately 1 kcal/mol too favorable. For the pure hexane-water interfacial simulations, we observe a monotonic decrease of the water dipole moment to near-vacuum values. This suggests that the electrostatic component of the desolvation free energy is not as severe for polarizable models than for fixed-charge force fields. The implications of such behavior pertain to the modeling of polar and charged solutes in lipidic environments.     

Processing of the molecular dynamics model by the parallel computer pax

Molecular dynamics model is processed by a parallel array type computer PAX, that has an architecture of nearest neighbor meash connection of processors. Two parallel schemes, named Lagrangian and Eulerian, are implemented, execution time and efficiency are analyzed and expressed in terms of the basic parameters such as problem size and array size. The Lagrangian scheme realizes high efficiency close to 1, which assures the linear speedup proportional to the size of the processor array. Parallel programming technique is also presented.     

Tensor3D: A computer graphics program to simulate 3D real-time deformation and visualization of geometric bodies

Tensor3D is a geometric modeling program with the capacity to simulate and visualize in real-time the deformation, specified through a tensor matrix and applied to triangulated models representing geological bodies. 3D visualization allows the study of deformational processes that are traditionally conducted in 2D, such as simple and pure shears. Besides geometric objects that are immediately available in the program window, the program can read other models from disk, thus being able to import objects created with different open-source or proprietary programs. A strain ellipsoid and a bounding box are simultaneously shown and instantly deformed with the main object. The principal axes of strain are visualized as well to provide graphical information about the orientation of the tensor's normal components. The deformed models can also be saved, retrieved later and deformed again, in order to study different steps of progressive strain, or to make this data available to other programs. The shape of stress ellipsoids and the corresponding Mohr circles defined by any stress tensor can also be represented. The application was written using the Visualization ToolKit, a powerful scientific visualization library in the public domain. This development choice, allied to the use of the Tcl/Tk programming language, which is independent on the host computational platform, makes the program a useful tool for the study of geometric deformations directly in three dimensions in teaching as well as research activities.     

MDWiZ: A platform for the automated translation of molecular dynamics simulations

A variety of popular molecular dynamics (MD) simulation packages were independently developed in the last decades to reach diverse scientific goals. However, such non-coordinated development of software, force fields, and analysis tools for molecular simulations gave rise to an array of software formats and arbitrary conventions for routine preparation and analysis of simulation input and output data. Different formats and/or parameter definitions are used at each stage of the modeling process despite largely contain redundant information between alternative software tools. Such Babel of languages that cannot be easily and univocally translated one into another poses one of the major technical obstacles to the preparation, translation, and comparison of molecular simulation data that users face on a daily basis. Here, we present the MDWiZ platform, a freely accessed online portal designed to aid the fast and reliable preparation and conversion of file formats that allows researchers to reproduce or generate data from MD simulations using different setups, including force fields and models with different underlying potential forms. The general structure of MDWiZ is presented, the features of version 1.0 are detailed, and an extensive validation based on GROMACS to LAMMPS conversion is presented. We believe that MDWiZ will be largely useful to the molecular dynamics community. Such fast format and force field exchange for a given system allows tailoring the chosen system to a given computer platform and/or taking advantage of a specific capabilities offered by different software engines.     

Some results of the interplay between computer graphics and mathematics

We show that computer graphics supports and visualizes mathematical research in the differential geometry of immersions and embeddings of surfaces in the three-dimensional space. Emphasis lies on the close connection between the mathematical questions, numerical approximations, and graphical investigations of surfaces which emerge from extremality principles, such as minimal surfaces.     

分子轨道对称性和反应机理的计算机模拟

以3DMAX和Visual Basic为主开发工具,制作了既有交互功能又有自播放功能的分子轨道对称性及其反应机理模拟的多媒体软件。介绍了软件的基本内容、设计思想、制作方法、关键技术、特点和功效。该软件充分应用计算机多媒体,特别是三维动画技术,反映分子轨道对称性和化学反应机理,有利于学习者对这些概念和理论更加直观、深入地认识。     

Molecular basis of agonicity and antagonicity in the androgen receptor studied by molecular dynamics simulations

Treatment of prostate cancer patients with antiandrogens is initially successful, though the therapy often becomes refractory over the time. This mechanism is not fully understood, but the presence of androgen receptor (AR) mutant forms which are activated by antiandrogens and other endogenous ligands, and overexpression of the receptor have been suggested. In an attempt to explain the molecular basis for agonicity and antagonicity in the androgen receptor, and the changes on biological activity of subtle modifications at the ligand and receptor (mutations) level, molecular dynamics simulations were performed on the androgen receptor wild type (WT), and T877A and W741 mutant forms, complexed with several non-steroidal androgens. The stabilizing role of residues from helices 3, 5, 11 and 12 was observed in non-steroidal androgens R-3, S-1, and R-bicalutamide and hydroxyflutamide in resistant mutations. In the AR WT antiandrogen R-bicalutamide complex, destabilization of M895 by both W741 and the sulfonyl linkage of the ligand may be responsible for reported antagonism. Changes in the ligand or mutations alleviating this effect were observed to stabilize the receptor in the active conformation, thus developing resistance to R-bicalutamide. The results presented provide a plausible explanation for the molecular basis of agonicity and antagonicity in the androgen receptor, and complement previous studies using static crystal structures, incorporating for the first time protein dynamics into the analysis. Thus, our results provide a valuable framework for the structure-based design of improved antiandrogens.     

The effects of instructional support and learner interests when learning using computer simulations

Within the scope of this study, the effectiveness of two kinds of instructional support was evaluated with regard to the learner’s interests. Two versions of a simulation program about the respiratory chain were developed, differing only in the kind of tasks provided for instructional support: One version contained problem-solving tasks, the other one contained worked-out examples. The focus was on the learner’s interest in the subject and in computers. The first goal of the study was to find to what extent computer simulations incorporating the different kinds of instructional support have positive effects on situational subject-interest. The second goal was to evaluate the interactions between the learner’s interests and the instructional support with regard to the learning results (subdivided into factual knowledge and understanding). Simulations with worked-out examples were shown to have positive effects on the learner’s situational interest in the subject. This was not found to be the case in simulations with problem-solving tasks. Regardless of the kind of instructional support, learners with little interest in the subject were able to achieve significant gains in factual knowledge. However, improvement in understanding was dependent on the kind of instructional support.     

Generation of interactive displays from FORTRAN using the PDP - 10/LDS-1 computer graphics system

The PDP-10/LDS-1 combination is a powerful and versatile computer graphics system. A package of programs described here permits the generation of displays and interaction with them by means of simple calls from FORTRAN programs. This makes computer graphics available to individuals who know a little FORTRAN but no assembler language. It serves also as a useful introduction to the LDS-1 for experienced programmers who intend to learn the assembler language and to write their own programs Experience with the language has shown that it is learnable quickly by the class of users at which it is aimed. In addition, the same package has been used by more experienced programmers as a powerful research tool in the study of conformations of biological macromolecules, such as proteins, DNA and RNA.