State of the art in studying protein folding and protein structure prediction using molecular dynamics methods

This study presents an overview of the state of the art in using molecular dynamics methods to simulate protein folding and in the end game of protein structure prediction. In principle, these methods should allow the highest level of detail possible and the highest accuracy, but they are limited by both the accuracy of the force field used in the simulation and the sampling possible in the available computer time. We describe current capabilities in running the simulations longer and more efficiently.     

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.     

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.     

分子动力学模拟蛋白质溶液吸附过程构象的变化

计算机模拟作为一种工具在药物分子设计、蛋白质工程、药物筛选等方面逐渐广泛应用起来。为了从分子水平上理解蛋白质吸附的机理,本文采用了刚体模型对聚十赖氨酸在固体表面吸附进行了分子动力学模拟。采用立方周期性边界条件,模拟在NVT条件下进行,各刚体的起始速度按Maxwell取样。初步研究了模拟过程中蛋白质构象的变化,跟踪了吸附过程中二面角φ和ψ的变化。研究结果表明,吸附过程中蛋白质二级结构发生了变化,C末端二级结构的变化最为明显。     

基于Oldroyd-B模型的弹性流体液滴动力学研究

本文采用Oldroyd-B模型对弹性流体中线串珠结构的动力学进行数学模拟。相对于牛顿流体而言,非牛顿流体液丝破裂过程非常缓慢。这种缓慢的破裂过程为流体提供了充足的时间显现一些有趣的现象,例如液滴的排泄和移动。通过主要作用力的总合近似分析液丝拉伸过程中的受力情况。弹性力在弹性液丝动力学中起重要作用,它显著阻碍了液丝从拉伸到排泄的变化过程。     

A discussion of the tribological phenomena under minimal load using molecular dynamics

This study explored the tribological phenomena under minimal load using molecular dynamics. In the simulation, <NVT> ensemble average standards and the Condensed-phase Optimized Molecular Potential for Atomistic Simulation Studies potential energy function were used. Regarding materials, this study used (5, 5) carbon nanotubes (CNTs) to move the copper atoms in order to obtain the coefficient of friction (COE) between the single-wall CNTs and copper atoms before analyzing the tribological phenomena under minimal load and changes in friction. This study found that, under an extremely tiny load, the direction of the resistance of the relative sliding is not always in the opposite direction of the movement direction. The influence of environment temperatures on the COE was that the environment temperature increases, the number of fluctuation also increases, but the COE reduces.     

共享存储环境下非平衡动力学方程组并行计算

OpenMP是现代多核机群系统采用的主要并行编程模型之一,在单CPU多核上可以获得良好的加速性能,但在整个机群系统上使用时,需要解决可扩展性差的问题.首先设计了求解非平衡动力学方程的并行算法.基于分布共享的多核机群系统,采用显式数据分布OpenMP并行计算方法,将数据进行分布式划分,分配到每个OpenMP线程,通过数据共享实现数据交换.计算结果表明显式OpenMP并行程序在保持可读性的同时,具有良好的可扩展性,在4核Xeon处理器构成的分布共享机群系统上,非平衡动力学方程组的数值并行计算可以扩展到1024个CPU核,具有明显的并行加速计算效果.     

复合推进剂颗粒填充模型的分子动力学模拟方法

将复合推进剂看作是颗粒与基体组成的复合材料,应用分子动力学模拟方法生成推进剂颗粒在基体中随机分布的填充模型。研究表明,分子动力学模拟方法,指定与颗粒直径成比例的增长率可有效地生成颗粒大小不等的填充模型,为分析推进剂细观力学性能和燃烧性能奠定基础。     

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.     

Improved dynamics model for human standing posture control using functional neuromuscular stimulation

Many studies on the use of functional neuromuscular stimulation for stabilizing the standing posture of paraplegic patients are conducted in computer simulations to minimize possible risks. Here, a five degrees of freedom skeletal-musculotendon muscle activation model of human body dynamics is formulated for the purpose of control effectiveness evaluation. By including the effect of arm rotation about the shoulder plus foot tipping about toe or heel in dynamics models, a more realistic response prediction capability can be achieved compared with previous models. A closed loop control simulation example is presented to demonstrate the significance of adding these features to the human body dynamics model.     

Introducing rotation invariance into the Neocognitron model for target recognition

This model introduces rotation invariance into the Neocognitron model by way of rotation layers. The most likely orientation of the target is detected and used for further pattern classification using an algorithm similar to that for the Neocognitron model. The visual target recognition capability of this model is demonstrated.     

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.     

Many-objective control optimization of high-rise building structures using replicator dynamics and neural dynamics model

Recently the authors presented a single-agent Centralized Replicator Controller (CRC) and a decentralized Multi-Agent Replicator Controller (MARC) for vibration control of high-rise building structures. It was shown that the use of agents and a decentralized approach enhances the vibration control system. Two key parameters in the proposed control methodologies using replicator dynamics are the total population (total available resources or the sum of actuators forces) and the growth rate. In the previous research, a sensitivity analysis was performed to determine the appropriate values for the population size and growth rate. In this paper, the aforementioned control methodologies are integrated with a multi-objective optimization algorithm in order to find Pareto optimal values for growth rates with the goal of achieving maximum structural performance with minimum energy consumption. A modified neural dynamic model of Adeli and Park is used in this research to solve the many-objective optimization problem where the Normal Boundary Intersection method is employed to find Pareto optimality. Sample results are presented using a 20-story steel benchmark structure subjected to historical and artificial accelerograms.     

Stable biased reduced order models using the Routh method of reduction

A generalization of the Routh method of reduction is introduced for obtaining stable reduced order models. The reduced models may be ‘ biased ’ in the sense that they may approximate the initial transient response of the high order system more closely than the steady-state response, and vice-versa. Given the desired order of the reduced model, the method of this paper produces a number of stable reduced models which approximate the high order system. The method is easily extended to multi-variable systems. Examples are given to illustrate the method and to make comparisons with other methods of reduction.     

Accurate and efficient methods for modeling colloidal mixtures in an explicit solvent using molecular dynamics

Most simulations of colloidal suspensions treat the solvent implicitly or as a continuum. However as particle size decreases to the nanometer scale, this approximation fails and one needs to treat the solvent explicitly. Due to the large number of smaller solvent particles, such simulations are computationally challenging. Additionally, as the ratio of nanoparticle size to solvent size increases, commonly-used molecular dynamics algorithms for neighbor finding and parallel communication become inefficient. Here we present modified algorithms that enable fast single processor performance and reasonable parallel scalability for mixtures with a wide range of particle size ratios. The methods developed are applicable for any system with widely varying force distance cutoffs, independent of particle sizes and independent of the interaction potential. As a demonstration of the new algorithm's effectiveness, we present results for the pair correlation function and diffusion constant for mixtures where colloidal particles interact via integrated potentials. In these systems, with nanoparticles 20 times larger than the surrounding solvent particles, our parallel molecular dynamics code runs more than 100 times faster using the new algorithms.     

MDMC: A molecular dynamics code for investigating the fragmentation dynamics of multiply charged clusters

MDMC² is a parallel code for performing molecular dynamics simulations on multiply charged clusters. It is a valuable complement to MCMC², a Monte Carlo program devoted to Monte Carlo simulations of multiply charged clusters in the NVT$NVT$ ensemble (Bonhommeau and Gaigeot, 2013). Both MCMC² and MDMC² codes employ a mesoscopic coarse-grained simplified representation of the clusters (or droplets): these clusters are composed of neutral and charged spherical particles/grains that may be polarisable. One grain can be either neutral or charged. The interaction potential is a sum of 2-body Lennard-Jones potentials (main cohesive contribution) and electrostatic terms (repulsive contribution), possibly supplemented by N$N$-body polarisation interactions. There is no restriction imposed on the values of the particle charges and/or polarisabilities. An external field can also be applied to the whole system. The derivatives of the potential energy-surface are determined analytically which ensures an accurate integration of classical equations of motion by a velocity Verlet algorithm. Conservation rules, such as energy conservation or centre-of-mass linear momentum conservation, can be steadily checked during the simulation. The program also provides some statistical information on the run and configuration files that can be used for data post-treatment. MDMC² is provided with a serial conjugate gradient program, called CGMC², that uses the same analytical derivatives as MDMC² and was found useful to probe the minima of the energy landscape explored during Monte Carlo or molecular dynamics simulations performed on multiply charged clusters.