Effect of the solvent on the conformational behavior of the alanine dipeptide deduced from MD simulations

In general, peptides do not exhibit a well-defined conformational profile in solution. However, despite the experimental blurred picture associated with their structure, compelling spectroscopic evidence shows that peptides exhibit local order. The conformational profile of a peptide is the result of a balance between intramolecular interactions between different atoms of the molecule and intermolecular interactions between atoms of the molecule and the solvent. Accordingly, the conformational profile of a peptide will change upon the properties of the solvent it is soaked. To get insight into the balance between intra- and intermolecular interactions on the conformational preferences of the peptide backbone we have studied the conformational profile of the alanine dipeptide in diverse solvents using molecular dynamics as sampling technique. Solvents studied include chloroform, methanol, dimethyl sulfoxide, water and N-methylacetamide. Different treatments of the solvent have been studied in the present work including explicit solvent molecules, a generalized Born model and using the bulk dielectric constant of the solvent. The diverse calculations identify four major conformations with different populations in the diverse solvents: the C₇^eq only sampled in chloroform; the C₅ or extended conformation; the polyproline (PII) conformation and the right-handed α-helix conformation (α_R). The results of present calculations permit to analyze how the balance between intra- and intermolecular interactions explains the populations of the diverse conformations observed.     

Modulating of the pnicogen-bonding by a H⋯π interaction: An ab initio study

An ab initio study of the cooperativity in XH₂P⋯NCH⋯Z and XH₂P⋯CNH⋯Z complexes (X = F, Cl, Br, CN, NC; Z = C₂H₂, C₆H₆) connected by pnicogen-bonding and H⋯π interactions is carried out by means of MP2 computational method. A detailed analysis of the structures, interaction energies and bonding properties is performed on these systems. For each set of the complexes considered, a favorable cooperativity is observed, especially in X = F and CN complexes. However, for a given X or Z, the amount of cooperativity effects in XH₂P⋯CNH⋯Z complexes are more important than XH₂P⋯NCH⋯Z counterparts. Besides, the influence of a H⋯π interaction on a P⋯N (C) bond is more pronounced than that of a P⋯N (C) bond on a H⋯π bond. The quantum theory of atoms in molecules shows that ternary complexes have increased electron densities at their bond critical points relative to the corresponding binary systems. The results also indicate that the strength of the P⋯N(C) and H⋯π interactions increases in the presence of the solvent.     

Combining molecular dynamics and lattice Boltzmann simulations: a hierarchical computational protocol for microfluidics

A hierarchical computational protocol is introduced to investigate the role of interfacial and wetting properties to the fluid displacement in hydrophilic pore network models (PNMs). Based on the combination of molecular dynamics (MD) and lattice Boltzmann method (LBM) simulations at both nano- and microscales, we study the role of dispersed functionalized \(\hbox {SiO}_{2}\) nanoparticles (NP) in brine to the oil displacement process in a clay (montmorillonite—MMT) pore structure. Our MD calculations indicate that dispersion of NP, with different hydrophilic properties, in brine solution reduces the interfacial tension between oil and brine, followed by an increase in the contact angle. The lowest interfacial tension and highest contact angle are for the hydrophilic NP functionalized with polyethylene glycol groups. By mapping the properties obtained from MD into LBM simulation parameters, we explore the oil displacement process in hydrophilic PNMs at the microscale. For all systems, the Young–Laplace filling rules are obeyed and, due to the finger formation, the displacement efficiency decreases as the capillary number increases. It was observed that, with the inclusion of NP, a reduction in interfacial tension associated with an increase in the contact angle may enhance the oil displacement process in hydrophilic pore systems at the microscale. The proposed computational protocol can be a versatile tool to explore the potentialities of chemical additives, such as NP, for the oil recovery process and investigate the effects of interfacial tension and wetting properties on the fluid behavior at both nano- and microscales.     

The effects of fluorine substitution on the chemical properties and inhibitory capacity of Donepezil anti-Alzheimer drug; density functional theory and molecular docking calculations

Drug fluorination has the potential to reproduce useful drugs with decreasing the side effect of them. Identifying the effect of this improvement on the chemical properties and biological interactions of drug symbolizes a meaningful progress in drug design. Here the fluorination of Donepezil as an anti-Alzheimer drug, including 7 fluorinated derivatives of it, was investigated computationally. In the first part of our calculations, the most important chemical properties of drug that affects the drug efficiency were investigated by applying the M06/6–31 g (d, p) and M062X/6–31 g (d, p) levels of theories. Findings showed that the fluorine substitution changed the drug stability as altered the solubility and molecular polarity. Furthermore, the intramolecular hydrogen bonding, charge distribution and electron delocalization of the drug were affected by this replacement. In the second section, the effect of fluorination on the drug⋯enzyme interactions was evaluated by using two effective methods Based on the molecular docking and density functional theory (DFT) calculations fluorine substitution influenced the Donepezil⋯Acetylcholinesterase interactions. Calculated binding energies by two computational methods displayed that the fluorine replacement changed the binding affinity of drug. Finally, the most significant non-bonded interactions between drugs and involved residues were investigated by bond length data analysis.     

Toward an ab initio potential energy surface for paclitaxel: A C-13 isoserine side chain conformational study

(S)-3-Methyl-3-butenyl-(2R,3S)-N-benzoyl-3-phenylisoserinate is used as a model of the C-13 side chain, an essential subunit for the cytotoxicity of the diterpenoid paclitaxel, a chemotherapeutic drug used in the treatment of cancer. The potential energy surface (PES), calculated using a density functional theory method (DFT) and refined with MP2 single-point energy calculations, based on B3LYP geometries, was evaluated. Twelve intramolecular hydrogen bond patterns were identified for 103 in vacuo conformers. The most stable subset of these structures was found to have cooperative NH ⋯ OH ⋯ OC(O) motifs and six minima of importance that lie within 1.2 kcal/mol of each other. The oxygen atoms of the ester groups effectively compete with the 2′-oxygen as a proton acceptor of NH to form stable internal hydrogen bonded structures. Additionally, the conventional OH ⋯ OC(N) hydrogen bond, which is represented by almost one third of the located minima, donates a number of stable conformers. However, the PES of the conformationally flexible model is highly dependent on the polarity of the environment. For example, the OH ⋯ OC(N) feature dominates over the cooperative motif in water. The side chain of the experimental T-taxol shaped structure agrees nicely with the respective theoretical lowest energy minimum. The π-π interactions of the phenyl rings and ethylene moiety of this structure are also discussed.     

QM/MM modeling of the hydrolysis and transfructosylation reactions of fructosyltransferase from Aspergillus japonicas,an enzyme that produces prebiotic fructooligosaccharide

Fructosyltransferases (FTs) act on sucrose by cleaving the β-(2 → 1) linkage, releasing glucose, and then transferring the fructosyl group to an acceptor molecule. These enzymes are capable of producing prebiotic fructooligosaccharides (FOSs) that are of industrial interest. While several FOS-synthesizing enzymes FTs have been investigated, their catalytic mechanism is not yet fully understood, especially the molecular details of how FOS are enzymatically synthesized from sucrose. Here, we present a comparative quantum mechanics/molecular mechanics (QM/MM) study on the hydrolysis and transfructosylation reactions catalyzed by A. japonicus FT using sucrose as donor and acceptor substrates. It is shown that the hydrolysis and transfructosylation reactions of the enzyme seem to be competitive with similar potential energy profiles. For all studied reaction steps, the fructosyl ring bound in the −1 position was observed to have a ⁴E conformation in the oxocarbonium ion-like transition state. Based on the SCC-DFTB/MM simulations of sucrose complexes of wildtype and D191A mutant FT, Asp191 is shown to be responsible for the productive sugar conformation (at subsite −1) required for catalysis. A key interaction, Asp119⋯nucleophile⋯1–OH (substrate), is proposed to facilitate the formation of fructosyl-enzyme intermediate. This is the first computational study for understanding the FOS synthesis process, and it can be applicable to related FOS-synthesizing enzymes.     

The equilibrium phase diagram of the pentaerythritol-pentaglycerine-2-amino-2methyl-1,3, propanediol (PE-PG-AMPL) system

Polyalcohols and amines have been considered as potential thermal energy storage materials, owing to their energetic solid-solid phase transitions. In this paper, we present equilibrium phase diagram of Pentaerythritol (PE)–Pentaglycerine (PG)– 2-amino-2methyl-1,3, propanediol (AMPL) ternary system that has been thermodynamically assessed using the CALPHAD method. A special class of, so called, “Plastic Crystals” have tetrahederally configured molecules with O–H⋯O or N–H⋯O layered or chained bonds in the low temperature phase, and store latent heat of transformation during solid-solid phase change in orientationally disordered crystals at higher temperatures. For example, in polyalcohols, there are O–H⋯O bond rotations around the C–C bonds that are responsible for storing large amounts of solid state phase change energy. Several binary equilibrium phase diagrams of polyalcohols, amines and combination thereof have been calculated and experimentally validated. We only know of three ternary phase diagram of these plastic crystals reported, to the best of knowledge. In the thermodynamic calculations of thePE-PG-AMPL system, we used the binary phase diagram experimental data for the optimization and calculation of excess energies. The binary systems have been optimized using regular and sub-regular solution models. The binaries as well as the ternary system have been calculated from room temperature to the liquid phase. The solution phases are modeled as substitutional solutions, in which the excess Gibbs energies are expressed by the Redlich–Kister–Muggianu polynomial. There is a very good agreement between previously reported experimental data and the calculated phase diagrams.     

Computation of eddy-current density on ESP motor and well casings under different operating conditions

This paper presents a 2D finite-element analysis of the induced eddy currents on motor and oil well casings of an electrical submersible pump (ESP) oil lifting system. Simulation results revealed that the increase in motor-casing conductivity and/or permeability decreases the eddy-current density on the well casing, contrary to that on the motor casing. Further increase in one or both of these parameters leads to a decrease in both current densities as a result of the skin effect phenomenon. However, the increase of well casing conductivity and/or permeability increases the eddy-current density on the well casing, while that on the motor casing remains unchanged. Increasing the fluid-mixture conductivity does not have any effect on the eddy-current density on the well casing, and for further increase in the fluid conductivity it decreases drastically, contrary to that on the motor casing which remains constant. The higher the current imbalance (including single phasing) and/or motor eccentricity, the higher is the maximum eddy-current density. Consequently, the increase of eddy-current density leads to an increase of the motor and well casings’ temperature, where the latter is known to accelerate the corrosion rate. It can be concluded that the design parameters and the construction of the motor and well casings play an important role in their corrosion.     

A theoretical survey of substituent effects on the properties of pnicogen and hydrogen bonds in cationic complexes of PH4+ with substituted benzonitrile

In this paper, we analyze the substituent effects on the nature and characteristics of P⋯N and H⋯N interactions in X-PhCN:PH₄⁺ complexes (X = H, F, Cl, Br, CN, NH₂, NO₂, CH₃ and N(CH₃)₂) as a working model at MP2(FC)/6-311++G(d,p) level of theory. The natural bond orbital (NBO) method as well as the quantum theory of atoms in molecules (AIM) is applied to characterize interactions in the studied complexes. In general, the pnicogen bonded systems are more stable than the corresponding hydrogen bonded cases. The strength of the interactions generally correlates well with the magnitudes of the negative electrostatic potentials of the nitrogen atom of isolated substituted benzonitrile (V_s,min(N)). The results indicate that increase in the electron withdrawing power of substituents is accompanied by decrease in the absolute value of V_s,min(N). Also, there are meaningful relationships between V_s,min(N) values and the results of AIM and NBO analyses in studied systems. Moreover, it is found that substituent effects on characteristics of P⋯N pnicogen and H⋯N hydrogen bonds can be expressed by Hammett constants.     

Understanding the effects of carbocyclic sugars constrained to north and south conformations on RNA nanodesign

Relatively new types of the modified nucleotides, namely carbocyclic sugars that are constrained to north or south (C2' or C3' exo) conformations, can be used for RNA nanoparticle design to control their structures and stability by rigidifying nucleotides and altering the helical properties of RNA duplexes. Two RNA structures, an RNA dodecamer and an HIV kissing loop complex where several nucleotides were replaced with north or south constrained sugars, were studied by molecular dynamics (MD) simulations. The substituted south constrained nucleotides in the dodecamer widened the major groove and narrowed and deepened the minor groove thus inducing local conformational changes that resemble a B-form DNA helix. In the HIV kissing loop complex, north and south constrained nucleotides were substituted into flanking bases and stems. The modified HIV kissing loop complex showed a lower RMSD value than the normal kissing loop complex. The overall twist angle was also changed and its standard deviation was reduced. In addition, the modified RNA dodecamer and HIV kissing loop complex were characterized by principal component analysis (PCA) and steered molecular dynamics (SMD). PCA results showed that the constrained sugars stabilized the overall motions. The results of the SMD simulations indicated that as the backbone δ angles were increased by elongation, more force was applied to the modified RNA due to the constrained sugar analogues.     

Characterization of slider-lubricant interaction with tribo-current

Lube-surfing recording combined with thermal fly-height control (TFC) technology is considered as a promising head-disk interface (HDI) scheme for further increasing magnetic areal density to 5?C10?Tbits/in². To realize this alternative technology, however, a lot of tricky issues are required to be solved. Among them, how to characterize the flying of slider in the lubricant or light lube-contact by the slider is probably one of the tough but inevitable challenges. In this study, the slider/lubricant/disk contact induced tribo-current is investigated with a modified media-tester in which the TFC slider is electrically isolated with the rest of the tester. The measured tribo-currents versus the heater voltages or the powers to the slider??s heater clearly indicate three different intensity regions of tribo-current, by which the three different contact types, namely, non-contact, lube-contact and solid-contact can be differentiated clearly. This method provides a promising way for accurately studying of lube-surfing recording.     

基于三维真实场景的落叶松林参数敏感性分析

森林冠层结构对太阳辐射能量有重要的影响,而双向反射率因子（BRF）在植被冠层反射研究中对冠层的生物物理特性起重要作用。本文在针叶树简化实验和落叶松模拟的基础上,分析了 BRF对落叶松及其环境参数的敏感性：叶面积指数(LAI)、太阳位置、地面背景和天空光比例。研究结果表明冠层的空间结构分布、地面背景的类型对BRF有很大的影响。     

五轴后置处理转角选解优化及奇异区域处理方法的研究

五轴后置处理是将CAM 软件系统产生的刀位文件转换成数控机床加工程序的关键 环节。基于五轴后置处理过程中转角选解、优化以及奇异区域加工数据处理的问题,提出了一种 集合转角选解、优化及奇异区域处理的方法,解决了因后置处理中选解不当引起的碰撞、旋转轴 在相邻刀位之间摆幅过大以及在奇异区域旋转轴产生急速转动、非线性误差过大等问题。该方法 应用C++语言开发了相应的后置处理系统,通过读取CATIA 刀位文件,生成可执行数控加工程 序,经Vericut 仿真验证该算法可行。     

基于OpenGL的静电喷涂雾化动画实现

通过对静电涂油机喷涂雾化的基本理论分析,模拟了油液在高压静电场中经过荷电区、射流区、波纹区、雾滴区和雾滴扩散区的动态雾化效果。结合粒子系统的基本思想,以射流长度和雾化角作为宏观特性描述了油液的雾化情况,使用Visual C++结合面向对象技术和OpenGL图形库,根据所建立的数学模型,模拟了不同电压下油液的静电雾化形态。将程序模拟图片与实验中得到图像相比较,其仿真结果基本反映了静电喷涂中油液雾化的过程,与实验观察的效果基本相符,它为研制新一代静电涂油机提供了理论基础。     

In silico activation of Src tyrosine kinase reveals the molecular basis for intramolecular autophosphorylation

Structural data suggest that important hinge-bending motions of the two lobes that shape the catalytic domain of Src tyrosine kinase, together with reorganization of an alpha helix (helix C), are needed for the activation loop to adopt the catalytically competent conformation. The phosphorylation of a Tyr residue (Tyr-416) in this loop also seems to be essential for enzyme activation. However, no information is available about the dynamics of this activation process. By comparing the inactive and active forms of the catalytic domains of Src and Lck, another member of the Src family, we first identified a short stretch that can act as a hinge for the interlobe motion. The opening of the lobes was then simulated using a targeted molecular dynamics approach. The results obtained suggested that pulling the two lobes apart is not enough to induce the required conformational change in the activation loop. Rather unexpectedly, however, swinging of the lobes situated Tyr-416 in a suitable position for intramolecular autophosphorylation, and further simulation of Tyr-416-phosphorylated Src in the presence of ADP did then result in a conformational change that placed the activation loop in a position similar to that found in the active open conformation of Lck. Taken together, our results establish a physical link between intramolecular autophosphorylation and loop activation.     

Electrokinetic motion of an electrically induced Janus droplet in microchannels

The electrokinetic motion of an electrically induced Janus oil droplet with one side covered with an aluminum oxide nanoparticle film in a circular microchannel was numerically simulated in this paper. The Janus oil droplet is electrically anisotropic as the nanoparticle-covered area carries positive charges and the rest oil–water surface area carries negative charges. A theoretical model was constructed to calculate the electrokinetic velocity of the Janus droplet by considering the force balance on the surface of the Janus droplet at steady state. In the model, the effects of the electric double layer and surface charges on the motion at the oil–water interface are considered. The effects of five parameters on the electrokinetic motion of the Janus droplets were studied: the electric field, the zeta potential ratio of the positively charged side to the negatively charged side of the Janus droplet, the viscosity ratio of the oil phase to the water phase, the nanoparticle coverage of the Janus droplet, and the size ratio of the diameter of the Janus droplet to the diameter of the cylindrical microchannel. The simulation results indicate that the increase in the electrical field, the zeta potential ratio, the viscosity ratio or the nanoparticle coverage leads to faster electrokinetic motion of the Janus droplet. On the other hand, with the increase in size ratio, the electrokinetic velocity of Janus droplet first decreases gradually then increases sharply. The simulated results were compared with the experimental results and good agreement was found.     

Assessment of sheet-metal bending requirements using neural networks

The springback behaviour of a sheet-metal is dependent on the properties of the metal and the bending conditions, namely the thickness of the sheet-metal, geometry of the tooling and the amount of force used for bending. Sheet-metal component manufacturing often requires near zero springback angle to obtain the correct shape of the product. An attempt has been made to model the non-linear relation between properties of the metal, the springback angle, geometry of the tooling and the bending force applied. Multilayer perceptron neural networks with a backpropagation learning algorithm were used to model the bending process. One set of data from bending experiments in a laboratory environment was used to train the networks. The networks were tested with the remaining set of experimental results. Then, the neural networks were used to predict the forces required for a number of bending experiments to achieve a zero springback angle. Validation of the neural network predictions was performed by trying to apply the predicted amounts of bending force in the physical experiments. The springback angles achieved were within ±1 degree, which is an acceptable range for the work. The research clearly demonstrates the applicability of neural networks to modelling the sheet-metal bending process.     

A Multiagent Evolutionary Algorithm for Combinatorial Optimization Problems

Based on our previous works, multiagent systems and evolutionary algorithms (EAs) are integrated to form a new algorithm for combinatorial optimization problems (CmOPs), namely, MultiAgent EA for CmOPs (MAEA-CmOPs). In MAEA-CmOPs, all agents live in a latticelike environment, with each agent fixed on a lattice point. To increase energies, all agents compete with their neighbors, and they can also increase their own energies by making use of domain knowledge. Theoretical analyses show that MAEA-CmOPs converge to global optimum solutions. Since deceptive problems are the most difficult CmOPs for EAs, in the experiments, various deceptive problems with strong linkage, weak linkage, and overlapping linkage, and more difficult ones, namely, hierarchical problems with treelike structures, are used to validate the performance of MAEA-CmOPs. The results show that MAEA-CmOP outperforms the other algorithms and has a fast convergence rate. MAEA-CmOP is also used to solve large-scale deceptive and hierarchical problems with thousands of dimensions, and the experimental results show that MAEA-CmOP obtains a good performance and has a low computational cost, which the time complexity increases in a polynomial basis with the problem size.