Collision-Induced Dissociation of Electrosprayed NaCl Clusters: Using Molecular Dynamics Simulations to Visualize Reaction Cascades in the Gas Phase

Infusion of NaCl solutions into an electrospray ionization (ESI) source produces [Na_(n+1)Cl _n ]⁺ and other gaseous clusters. The n?=?4, 13, 22 magic number species have cuboid ground state structures and exhibit elevated abundance in ESI mass spectra. Relatively few details are known regarding the mechanisms whereby these clusters undergo collision-induced dissociation (CID). The current study examines to what extent molecular dynamics (MD) simulations can be used to garner insights into the sequence of events taking place during CID. Experiments on singly charged clusters reveal that the loss of small neutrals is the dominant fragmentation pathway. MD simulations indicate that the clusters undergo extensive structural fluctuations prior to decomposition. Consistent with the experimentally observed behavior, most of the simulated dissociation events culminate in ejection of small neutrals ([NaCl] _i , with i?=?1, 2, 3). The MD data reveal that the prevalence of these dissociation channels is linked to the presence of short-lived intermediates where a relatively compact core structure carries a small [NaCl] _i protrusion. The latter can separate from the parent cluster via cleavage of a single Na-Cl contact. Fragmentation events of this type are kinetically favored over other dissociation channels that would require the quasi-simultaneous rupture of multiple electrostatic contacts. The CID behavior of NaCl cluster ions bears interesting analogies to that of collisionally activated protein complexes. Overall, it appears that MD simulations represent a valuable tool for deciphering the dissociation of noncovalently bound systems in the gas phase.

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自组装的分子动力学模拟

简要回顾了近年来国内外分子动力学模拟自组装的研究,对已报道的建模方法、可视化表现以及相关应用略作概述,并以此为基础对自组装过程的分子动力学模拟研究所面临的问题和尚需深入的内容进行了讨论。基于自组装、相变和涨落的固有联系,提出了以研究波动为手段,和以频率相关热容为研究对象的探索方向。希望能够为分子动力学模拟推动自组装研究提供有益的参考。     

Molecular Simulations in Materials Science

正Molecular simulation finds application in a wide range of research fields based on life and materials sciences.It helps comprehend and predict the chemical and physical properties of substances;thus,it is useful in directing RD and industrial production.In this special issue,we focus on molecular simulations in material sciences.     

Molecular Simulations in Macromolecular Science

Chinese Journal of Polymer Science - Molecular simulations are now an essential part of modern chemistry and physics, especially for the investigation of macromolecules. They have evolved into...     

分子聚集体的光谱模拟

采用Frenkel激子理论研究了一维线性和二维人字形分子聚集体的吸收和发射光谱.通过引入激子离域长度的概念,将聚集体与单分子的光谱线形函数联系起来.计算的光谱结果表明,聚集体的光谱与分子在聚集体中的排列紧密相关.分析了一维J聚集光谱发生红移以及二维人字形分子聚集体吸收光谱形成J和H激子谱带的内在原因.模拟得到的聚集体的...     

甲硫氨酸-脑啡肽的分子动力学模拟

The conformational properties of Met-enkephalin (Tyr-Gly-Gly-Phe-Met) were investigated by high temperature quenched molecular dynamics simulations in vapor. Each of these selected structures were then analyzed according to their backbone(φ,Ψ) conformational distributions and sorted into 13 families by computing the rms difference between the Cα-C backbone fragments of each residue over all the structures. Selected lowest energy conformations from each of 13 families were thoroughly energy minimized. The results of simulations show that Met-enkephalin is a flexible molecule. It shows a type Ⅰβ-turn, with the Gly2 carbonyl forming a hydrogen bond with the Met5 amino proton and a type Ⅱβ turn, with the Tyr1 amino proton forming a hydrogen bond with the Phe4 carbonyl. The multiple fit were carried out for all of the 13 conformers with morphine(9 atoms on the pharmacophore groups). F2 and F6 were the most similar to morphine. The rms were 0.0504 nm and 0.0726 nm. The results of simulations also show that Tyr amino N corresponds to N on piperidine ring in morphine, Tyr phenol corresponds to the phenol in morphine, the aromatic ring of Phe corresponds to the cyclohexene ring in morphine. The distances between the three pharmacophores, d1 (Tyr N to Tyr OH), d2 (Tyr N to Tyr du1), d3(Tyr N to Phe du2) and d4(Tyr N to Phe du2) were found to be about 0.8, 0.5, 0.7-0.9 and 0.5 nm, respectively, the corresponding, distances of morphine were found to be 0.7697(N18 to O6),0.5143(N18 to du25), 0.3962(N18 to du24)和0.5566(N18 to O15)nm. Therefore, they may be acted on the same receptor. This model should aid in pharmaceutical design of peptide and nonpeptide ligands with opioid.     

Molecular Simulations using Spherical Harmonics

Computer-aided drug design is to develop a chemical that binds to a target macromolecule known to play a key role in a disease state. In recognition of ligands by their protein receptors, molecular surfaces are often used because they represent the in-teracting part of molecules and they should reflex the comple-mentarity between ligand and receptor. However, assessing the surface complementarity by searching all relative position of two surfaces is often computationally expensive. The comple-mentarity of lobe-hole is very important in protein-ligand inter-actions. Spherical harmonic models based on expansions of spherical harmonic functions were used as a f‘mgerprint to ap-proximate the binding cavity and the ligand, respectively. This defines a new way to identify the complementarity between lobes and holes. The advantage of this method is that two spherical harmonic surfaces to be compared can be defined sep-arately. This method can be used as a filter to eliminate candi-dates among a large number of conformations, and it will speed up the docking procedure. Therefore, it is possible to select complementary ligands or complementary conformations of a ligand and the macromolecules, by comparing their fingerprints previously stored in a database.     

Molecular Dynamics Simulations of Polymer Translocations

Summary: Molecular dynamics simulation studies of the translocation of charged homopolymers of length, N, driven by an electric potential gradient through a channel have been performed. We find that the translocation time, τ, displays an inverse power dependence on the temperature of the simulation τ ∼ (T − T₀)^−7/4, which is in very good agreement with experimental results. In addition, the dependence of τ on the driving field strength and the velocity of translocation on the polymer length N have also been obtained. The results suggest that such minimalist models are useful in modelling biological processes and that the molecular dynamics method is a suitable approach for carrying out these simulations.

Snapshot of the polymer during the simulation.     

Molecular Dynamics Simulations of Energetic Solids

A continuing objective in the area of energetic materials is to reduce sensitivity toward impact and shock. One approach is to develop a better understanding of how factors related to the crystal lattice, e.g., defects, influence the initiation and propagation of detonation. Molecular dynamics is a useful tool for this purpose. This paper presents an overview of molecular dynamics treatments of energetic solids. Some of these have simulated initiation and propagation in idealized systems; others have focused on developing a satisfactory procedure for describing molecular crystals of practical significance. Our emphasis in this discussion is on the progress that has been made along the second lines.     

Molecular Simulations and Drug Discovery of Adenosine Receptors

G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins. Four subtypes of adenosine receptors (ARs), the A₁AR, A_2AAR, A_2BAR and A₃AR, each with a unique pharmacological profile and distribution within the tissues in the human body, mediate many physiological functions and serve as critical drug targets for treating numerous human diseases including cancer, neuropathic pain, cardiac ischemia, stroke and diabetes. The A₁AR and A₃AR preferentially couple to the G_i/o proteins, while the A_2AAR and A_2BAR prefer coupling to the G_s proteins. Adenosine receptors were the first subclass of GPCRs that had experimental structures determined in complex with distinct G proteins. Here, we will review recent studies in molecular simulations and computer-aided drug discovery of the adenosine receptors and also highlight their future research opportunities.     

分子模拟中的增强抽样方法

分子模拟在化学、物理、生物、材料等多学科的发展中起着越来越重要的作用。然而,受到当前计算机处理速度的限制,分子模拟计算所能够达到的时间尺度同实验或实际应用中要求的时间尺度相比还存在着巨大的差距。增强抽样方法的发展和应用可以有效地拓宽分子模拟所能研究体系的时间尺度,极大地提高分子模拟的热力学和动力学计算能力。本文中先简单介绍增强抽样方法的发展以及几类增强抽样方法的优缺点,然后重点介绍了我们研究组所发展的温度积分抽样方法(Integrated Tempering Sampling, ITS)的基本思路及其在蛋白质折叠研究中的应用。文章最后总结了增强抽样方法发展的新需求,同时也对此研究方向的广阔发展前景进行了展望。     

八硝基立方烷高温热分解分子动力学模拟

随着对高能量密度材料的性能要求不断提高,新型高能量密度材料成为近期研究热点,其中八硝基立方烷(ONC)由于其优越的性能成为其中典型的代表,然而关于八硝基立方烷热分解的动力学机理研究比较少。本文采用ReaxFF反应力场模拟高温条件下凝聚相八硝基立方烷初始热分解过程。研究发现热分解过程中八硝基立方烷笼状骨架结构中C-C键最先发生断裂,并逐步破坏形成八硝基环辛烯等,随后出现NO₂和O等,计算结果表明笼状骨架结构的破坏存在三种不同路径。八硝基立方烷在高温条件下热分解的主要产物有NO₂、O₂、CO₂、N₂、NO₃、NO、CNO以及CO等,其中N₂和CO₂是终态产物,不同温度对产物均产生不同程度的影响。     

端羟基聚丁二烯/增塑剂共混物相容性的分子动力学模拟和介观模拟

应用分子动力学(MD)和介观动力学(MesoDyn)模拟方法对固体推进剂中端羟基聚丁二烯(HTPB)与增塑剂癸二酸二辛酯(DOS)、硝化甘油(NG)的相容性进行了研究. 采用MD模拟方法在COMPASS力场下, 对纯物质、HTPB/增塑剂共混物的密度、内聚能密度、溶度参数和共混物分子间的Flory-Huggins作用参数及结合能等进行了模拟计算, 通过比较溶度参数差值(Δδ)的大小、模拟前后体系密度变化情况均可以预测HTPB与增塑剂的相容性, 结合能的分析揭示了HTPB/增塑剂共混物组分间的相互作用及本质. 将Flory-Huggins作用参数转化为MesoDyn模拟的输入参数, 采用MesoDyn模拟方法对HTPB/增塑剂共混体系的介观形貌与动力学演变过程进行了研究, 通过模拟得到的等密度图、自由能密度和有序度参数等可以判断共混体系的相容性. MD和MesoDyn模拟结果均表明: HTPB/DOS属于相容体系, 而HTPB/NG属于不相容体系, 其结论与实验结果一致.     

Dissipative Particle Dynamics Simulations of Polymer Brushes: Comparison with Molecular Dynamics Simulations

Summary: The structure of polymer brushes is investigated by dissipative particle dynamics (DPD) simulations that include explicit solvent particles. With an appropriate choice of the DPD interaction parameters , we obtain good agreement with previous molecular dynamics (MD) results where the good solvent behavior has been modeled by an effective Lennard–Jones potential. The present results confirm that DPD simulation techniques can be applied for large length scale simulations of polymer brushes. A relation between the different length scales and is established.

Polymer brush at a solid–liquid interface.     

洋刀豆脲酶与抑制剂相互作用的分子对接和分子动力学研究

通过洋刀豆脲酶抑制剂的筛选实验得到具有较好抑制活性的化合物2-乙酰基-γ-丁内酯(COM), 其半数抑制浓度在微摩尔浓度级别(IC₅₀＝375 μmol•L^－l). 在此基础上, 使用分子对接和分子动力学(MD)模拟的方法研究洋刀豆脲酶与抑制剂乙酰氧肟酸(AHA)及活性化合物COM之间的相互作用. 用Gold3.0程序将两个小分子与洋刀豆脲酶的晶体结构进行对接, 对接得到的复合物模型使用Amber程序进行MD模拟研究. 模拟过程中, 脲酶结构中的双核镍离子活性中心选用non-bonded模型. 研究结果显示: AHA与洋刀豆脲酶结合时, Ni(1)和Ni(2)均为五配位|COM与洋刀豆脲酶结合时Ni(1)为五配位, Ni(2)为六配位的结合模型更加合理. 这些研究为了解洋刀豆脲酶与抑制剂之间的相互作用提供了重要的参考信息.     

液态合金NiAl凝固过程中微观结构转变的分子动力学模拟

采用分子动力学模拟方法对液态NiAl凝固过程进行了研究,考察了不同冷却速度下液态NiAl结构变化特点,原子间相互作用势采用F-S多体势,结构分析采用键取向序和对分析技术.计算结果表明,冷却速度对液态NiAl结构转变有重要影响,在不同的冷却速度下, NiAl凝固过程出现了明显不同,冷速为4×1013和4×1012 K/s时, NiAl快速凝固为无序的非晶体结构;而在较慢的8×1011 K/s冷速下, NiAl凝固为晶态结构.给出了不同冷却速度下液态NiAl结构转变的微观信息.     

DNA与二脒DB293复合物的分子动力学模拟

采用分子动力学模拟了DNA小沟与芳香二脒化合物DB293结合形成的复合物,通过5ns的模拟研究表明,DB293分子可紧密结合在DNA的AATT小沟区域,和双螺旋d[CGCGAATTCGCG]2形成稳定的复合物。DB293苯并咪唑的氮原子N2能够与DNA胸腺嘧啶碱基T7的O2原子和T19的O2原子形成两个较强的氢键,同时,其末端氨基的N3原子和T20的O2原子形成一个较弱的氢键。本文在分子水平上提供了DB293直接与双螺旋DNA相互作用的结构及复合物的动态变化情况,为设计出更高活性的芳香二脒类DNA小沟结合剂提供一定的理论依据。     

表面活性剂界面自组装的分子动力学模拟

主要介绍了表面活性剂在液／液、气／液和固／液界面的自组装,详细讨论了分子动力学模拟在表面活性剂界面自组装体系的应用,指出了近年来该领域的发展现状及应用前景。     

Molecular Dynamics Simulations for Ice Modifications II and IX

Molecular vibrations of water (H₂O and D₂O) in crystals of ice II and ice IX are studied by molecular dynamics in a rigid bond approximation with a fixed bond angle. Using an atom-atomic potential PM for describing the interactions between water molecules in ice II (N = 576 molecules) and ice IX (N = 768) in an NVE ensemble leads to reproduction of the structure of both types of ice. For all water molecules and separately for each system of crystallographically equivalent water molecules in ice crystals, we defined the time dependence of the mean-square displacement of the center of mass of the molecule, the autocorrelation function of velocity for the center of mass, and the autocorrelation function of velocity for hydrogen (deuterium) atoms. The densities of vibrational states are calculated as Fourier integrals of the corresponding autocorrelation functions. In the case of ice II, the densities of states agree well with the experimental incoherent inelastic neutron scattering spectra. In the case of ice IX, agreement is worse. For both polymorphs, the mean-square displacement and the densities of vibrational states of the center of mass of the molecule and the hydrogen (deuterium) atom differ slightly between molecules belonging to different systems of crystallographic positions. This is explained by the difference in their environments.