腺苷酸激酶催化循环后期Mg^(2+)转移的分子动力学模拟（英文）

腺苷酸激酶是一个包含三个结构域(LID结构域、NMP结构域和CORE结构域)的蛋白质分子,其主要作用是催化化学反应Mg^(2+)+ATP+AMP(?)2ADP+Mg^(2+)进而将细胞内ATP分子的浓度维持在合适的范围内。在腺苷酸激酶催化上述化学反应的过程中,需要有Mg^(2+)的参与。最近的实验发现Mg^(2+)不仅参与上述反应的化学步骤,而且对化学反应发生后底物的释放过程至关重要。己有晶体结构数据显示,在催化循环过程的化学反应步骤完成后,一个Mg^(2+)可同时和分别位于LID结构域及NMP结构域的两个ADP分子配位。然而,在底物的释放与分离过程中,Mg^(2+)可能只与其中一个ADP分子结合。由于Mg^(2+)与ADP分子的结合情况会在很大程度上影响作为催化循环限速步骤的底物释放过程,因此人们有必要研究清楚在底物释放前Mg^(2+)与催化产物ADP分子的配位情况,即Mg^(2+)更倾向于与LID结构域的ADP分子结合还是与NMP结构域的ADP分子结合。本文中,我们对催化反应后底物释放前的酶-底物复合物(包含酶、两个ADP分子以及Mg^(2+))做了分子动力学模拟研究。我们基于metadynamics方法得到了Mg^(2+)在两个ADP分子间转移的自由能面,发现在底物分离与释放过程中,Mg^(2+)更倾向于与LID结构域的ADP分子结合。只有当LID结构域的ADP分子被质子化,同时NMP结构域的ADP分子处于去质子化状态时,Mg^(2+)才会倾向于与NMP结构域的ADP分子结合。另外,我们也刻画了Mg^(2+)转移过程中配体交换与脱水过程。本工作的研究结果有助于理解腺苷酸激酶催化循环后期的分子过程。

Advances in Enhanced Sampling Molecular Dynamics Simulations for Biomolecules

Molecular dynamics simulation has emerged as a powerful computational tool for studying biomolecules as it can provide atomic insights into the conformational transitions involved in biological functions.However,when applied to complex biological macromolecules,the conformational sampling ability of conventional molecular dynamics is limited by the rugged free energy landscapes,leading to inherent timescale gaps between molecular dynamics simulations and real biological processes.To address this issue,several advanced enhanced sampling methods have been proposed to improve the sampling efficiency in molecular dynamics.In this review,the theoretical basis,practical applications,and recent improvements of both constraint and unconstrained enhanced sampling methods are summarized.Furthermore,the combined utilizations of different enhanced sampling methods that take advantage of both approaches are also briefly discussed.

Molecular dynamics simulations of ovalbumin adsorption at squalene/water interface

The adsorption of protein molecules to oil/water(O/W)interface is of critical importance for the product design in a wide range of technologies and industries such as biotechnology,food industry and pharmaceutical industry.In this work,with ovalbumin(OVA)as the model protein,the adsorption conformations at the O/W interface and the adsorption stability have been systematically studied via multiple simulation methods,including all-atom molecular dynamic(AAMD)simulations,coarse-grained molecular dynamic(CGMD)simulations and enhanced sampling methods.The computational results of AAMD and CGMD show that the hydrophobic tail of OVA tends to be folded under long time relaxation in aqueous phase,and multiple adsorption conformations can exist at the interface due to heterogeneous interactions raising from oil and water respectively.To further study the adsorption sites of the protein,the adsorption kinetics of OVA at the O/W interface is simulated using metadynamics method combined with CGMD simulations,and the result suggests the existence of multiple adsorption conformations of OVA at interface with the head-on conformation as the most stable one.In all,this work focuses on the adsorption behaviors of OVA at squalene/water interface,and provides a theoretical basis for further functionalization of the proteins in emulsion-based products and engineering.

Metadynamic Recrystallization of the As-cast 42CrMo Steel after Normalizing and Tempering during Hot Compression

The existing researches of hot ring rolling process are mainly based on forged billet. Compared with the existing process, the new ring casting-rolling compound forming process has significant advantages in saving materials and energy, reducing emission and reducing the production cost. The microstructure evolution of the casting materials during hot deformation is the basis of the research of the new process. However, the researches on the casting materials are rare. The metadynamic recrystallization of the as-cast 42CrMo steel after normalizing and tempering during the hot compression is investigated. The tests are performed on the Gleeble-1500 thermal-mechanical simulator. The influence rule of the deformation parameters on the metadynamic recrystallization is obtained by analyzing the experimental data. The kinetic model of the rnetadynamic recrystallization is deduced. The analysis results show that the metadynamic recrystallization fraction increases with the increase of the deformation temperature and the strain rate. The metallographic experiments are used to investigate the influence rule of the deformation parameters on the grain size of the metadynamic recrystallization. The experimental results show that the grain of the metadynamic recrystallization could be refined with the increase of the strain rate and the decrease of the deformation temperature during hot compression. The occurrence of the metadynamic recrystallization during the hot deformation is more difficult in as-cast 42CrMo steel than in forged 42CrMo steel. The research can provide the foundation for the further research of the hot deformation behaviors of the as-cast structure and theoretical support for the new ring casting-rolling compound process.

Modeling of metadynamic recrystallization kinetics after hot deformation of low-alloy steel Q345B

Based on the steady-state strain measured by single-pass hot compression tests,the method by a double-pass hot compression testing was developed to measure the metadynamic-recrystallization kinetics.The metadynamic recrystallization behavior of low-alloy steel Q345B during hot compression deformation was investigated in the temperature range of 1 000-1 100℃,the strain rate range of 0.01-0.10 s -1 and the interpass time range of 0.5-50 s on a Gleeble-3500 thermo-simulation machine.The results show that metadynamic recrystallization during the interpass time can be observed.As the deformation temperature and strain rate increase,softening caused by metadynamic recrystallization is obvious.According to the data of thermo-simulation,the metadynamic recrystallization activation energy is obtained to be Qmd=100.674 kJ/mol and metadynamic recrystallization kinetics model is set up.Finally,the error analysis of metadynamic recrystallization kinetics model proves that the model has high accuracy(correlation coefficient R=0.988 6).

Microstructural evolution of a superaustenitic stainless steel during a two-step deformation process

Single-and two-step hot compression experiments were carried out on 16Cr25Ni6Mo superaustenitic stainless steel in the temperature range from 950 to 1150°C and at a strain rate of 0.1 s^（-1）. In the two-step tests, the first pass was interrupted at a strain of 0.2; after an interpass time of 5, 20, 40, 60, or 80 s, the test was resumed. The progress of dynamic recrystallization at the interruption strain was less than 10%. The static softening in the interpass period increased with increasing deformation temperature and increasing interpass time. The static recrystallization was found to be responsible for fast static softening in the temperature range from 950 to 1050°C. However, the gentle static softening at 1100 and 1150°C was attributed to the combination of static and metadynamic recrystallizations. The correlation between calculated fractional softening and microstructural observations showed that approximately 30% of interpass softening could be attributed to the static recovery. The microstructural observations illustrated the formation of fine recrystallized grains at the grain boundaries at longer interpass time. The Avrami kinetics equation was used to establish a relationship between the fractional softening and the interpass period. The activation energy for static softening was determined as 276 kJ/mol.

Investigation into the stress-strain curves of deformation-induced ferrite transformation in a low carbon steel

A series of tests of deformation-induced ferrite transformation （DIP-T） in a low carbon steel were carried out by the Gleeble-3500 hot simulation machine at a temperature range of Ae3-Ar3. The overall stress-strain curves during DIFT can be divided into three typical types： ＂double-humped＂,＂ single-humped＂ and ＂transitional＂. The peaks exhibited in the curve are involved with deformation-induced transformation which happened in grains or at the grain boundaries. According to the stress-time curve and strain-time curve, strain capacity dramatically postponed the strain-induced transformation, which leads to the start of the transformation right ahead of the finish of deformation and the majority of the ferrite transformation process mainly happened after the deformation. Deformation-induced transformation is a metadynamic transformation process with dynamic nucleation.

Enhanced Sampling Simulations on Transition-Metal-Catalyzed Organic Reactions:Zirconocene-Catalyzed Propylene Polymerization and Sharpless Epoxidation

The bond breaking and forming in chemical reactions is a typical rare event,which is one of the difficult problems in molecular dynamics simulations.Numerous enhanced sampling methods have been developed to extend the time scale covered by molecular simulations.However,the difficulties of obtaining appropriate collective variables from complicated reaction pathways and a controlled sampling over the desired phase space remain as challenges.Herein,we use MetaITS,which combines metadynamics and integrated tempered sampling,to increase the sampling efficiency for chemical reactions.Metadynamics with collective variables obtained by harmonic linear discriminant analysis can efficiently decrease the main energy barrier of chemical reaction.Meanwhile,integrated tempered sampling can enhance the exploration of other degrees of freedom.In this study,we applied the MetaITS method to two transition-metal-catalyzed organic reactions with complicated reaction coordinates.We simulated here a zirconocene-catalyzed propylene polymerization to investigate the regioselectivity and temperature effects.We also studied a Sharpless epoxidation reaction,for which both chiral products are observed through simulation.

Static recrystallization behaviors and mechanisms of 7Mo super-austenitic stainless steel with undissolved sigma precipitates during double-stage hot deformation

Static recrystallization(SRX)behaviors and corresponding recrystallization mechanisms of 7Mo super-austenitic stainless steel were studied under different deformation conditions.The order of influence of deformation parameters on static recrystallization behaviors,from high to low,is followed by temperature,first-stage strain and strain rate.Meanwhile,the effect of holding time on static recrystallization behaviors is significantly controlled by temperature.In addition,with the increase in temperature from 1000 to 1200°C,the static recrystallization mechanism evolves from discontinuous static recrystallization and continuous static recrystallization(cSRX)to metadynamic recrystallization and cSRX,and finally to cSRX.The cSRX exists at all temperatures.This is because high stacking fault energy(56 mJ m−2)promotes the movement of dislocations,making the deformation mechanism of this steel is dominated by planar slip of dislocation.Large undissolved sigma precipitates promote static recrystallization through particle-stimulated nucleation.However,small strain-induced precipitates at grain boundaries hinder the nucleation of conventional SRX and the growth of recrystallized grains,while the hindering effect decreases with the increase in temperature.

重要性采样方法与自由能计算

分子动力学模拟与自由能计算已经在化学、生物学与材料学等领域得到广泛的应用。然而,由于在传统分子动力学模拟的时间尺度内,体系很难跨越较高的自由能能垒,在相空间内的采样大大受限,采样困难使自由能计算难以收敛。增强采样是解决这一问题的有效途径,重要性采样方法就是其中一类。本文综述了四种广泛应用的重要性采样方法——伞状采样方法、metadynamics方法、自适应偏置力方法和温度加速分子动力学方法的原理和进展,其中重点概述了自适应偏置力方法的最新发展——扩展自适应偏置力方法和扩展广义自适应偏置力方法,并对这四种重要性采样方法的优缺点进行了比较。最后,讨论和展望了重要性采样与自由能计算方法面临的挑战和前景,并提出了对自适应偏置力方法可能的改进,如与加速分子动力学(aMD)或弦方法结合以提高在高维度空间中的采样效率。

Atomistic simulation of the coupled adsorption and unfolding of protein GB1 on the polystyrenes nanoparticle surface

Understanding the processes of protein adsorption/desorption on nanopartieles＇ surfaces is important for the development of new nanotechnology involving biomaterials; however, an atomistic resolution picture for these processes and for the simultaneous protein conformational change is missing. Here, we report the adsorption of protein GB 1 on a polystyrene nanoparticle surface using atomistic molecular dynamic simulations. Enabled by metadynamics, we explored the relevant phase space and identified three protein states, each involving both the adsorbed and desorbed modes. We also studied the change of the secondary and tertiary structures of GB 1 during adsorption and the dominant interactions between the protein and surface in different adsorption stages. The results we obtained from simulation were found to be more adequate and complete than the previous one. We believe the model presented in this paper, in comparison with the previous ones, is a better theoretical model to understand and explain the experimental results.

Enhanced sampling based on slow variables of trajectory mapping

Most current enhanced sampling(ES) algorithms attempt to bias a potential energy surface based on preset slow collective variables to improve simulation efficiency. However, due to difficulty in obtaining slow variables in complex molecular systems,approximate slow variables are usually applied in ES, which often fail to achieve the expected high efficiency and sufficient accuracy when reconstructing equilibrium properties. In this paper, we demonstrate that the trajectory mapping(TM) technique has the potential to provide the required slow variables for ES. We illustrate the application of a typical ES algorithm(metadynamics)based on the slow variables constructed from the TM in a hairpin peptide system. In this system, both the equilibrium properties and slow dynamics are accurately obtained within approximately two to three orders of magnitude shorter simulation time than in regular molecular dynamics simulation.

Effects of holding time and Zener-Hollomon parameters on deformation behavior of cast Mg-8Gd-3Y alloy during double-pass hot compression

Double-pass hot compression tests were carried out over a wide range of holding time（0–180 s） and Zener-Hollomon parameter（1.6 E15–1.3 E20） to study the deformation behavior of cast Mg-8 Gd-3 Y alloy.The flow curves show obvious work hardening and strain softening stages, leading to the peak stress of double-pass hot compression. Holding time and Zener-Hollomon parameter can significantly affect the second pass peak stress. It is found that increasing the holding time can cause a higher peak stress in the second pass deformation. The second pass stress reaches the peak stress of 71 MPa at ZenerHollomom parameter of 1.6 E15. When the parameter rises to 1.3 E20, the second pass peak goes up to237 MPa. In addition, the second pass peak stress is significantly higher than the unloading stress, which is opposite to the flow behavior of aluminum alloys. Residual stored deformation energy caused by the first pass deformation could be consumed by metadynamic recrystallization. Therefore, more strain energy is required for subsequent dynamic recrystallization, resulting in hardening behavior. A hardening fraction is defined to describe the deformation behavior quantitatively, which shows a positive correlation with the metadynamic recrystallization fraction. The metadynamic recrystallization leads to grain growth at the inter pass holding stage, diminishing dynamic recrystallization nucleation positions in the second pass deformation.

Metadynamic Recrystallization Behavior of As-cast 904L Superaustenitic Stainless Steel

The metadynamic recrystallization （MDRX） behavior of as-cast 904L superaustenitic stainless steel was in- vestigated by double pass isothermal compression tests at temperatures of 950-1 150 ℃, strain rates of 0.05-5 s 1 and interval of 1-100 s. The effects of working parameters （deformation temperature, strain rate, pre-strain and in- terval time） on the flow curves and microstructural evolution were discussed. The MDRX fraction increased obvious- ly with the increase of deformation temperature, strain rate and interval time. The MDRX softening was controlled by the migration of grain boundary, annihilation of dislocation and dynamic recrystallization. Moreover, the kinetic model was established for the prediction of MDRX behavior of as-cast 904L superaustenitic stainless steel based on the experimental data. A good agreement between the predicted and the experimental values was achieved （correla- tion coefficient R2= 0.98）, indicating a satisfactory accuracy.

Metadynamic recrystallization behaviors of SA508Gr.4N reactor pressure vessel steel during hot compressive deformation

The metadynamic recrystallization(MDRX)model is established,and the coefficients determined by multiple linear regression analysis are used to describe the microstructure evolution of SA508Gr.4N steel.The effects of compression temperature of 950–1150℃,strain rate of 0.001–0.1 s^(-1),pre-strain of 0.3–0.6,initial austenite grain size(IAGS)of 136–552 lm,and interval time of 1–300 s on the MDRX kinetics and microstructure evolution were analyzed,using twopass compression test method on Gleeble thermo-mechanical simulator.The results show that MDRX kinetics and austenite grain size are strongly dependent on compression temperature and strain rate,MDRX volume fraction increases with increasing compression temperature and strain rate,and the grain size decreases with increasing strain rate and decreasing compression temperature,while less affected by the pre-strain and IAGS.Meanwhile,the values predicted using MDRX model and the ones calculated from experiment are compared,and the results show that the proposed model can give a reasonable estimate of MDRX behavior for SA508Gr.4N steel.

Static and Metadynamic Recrystallization of Low Carbon Steels During Mechanical Deformation

Static and metadynamic recrystallization models were developed with the coefficients determined by multiple nonlinear regression analyses to describe microstructure evolution in low carbon steels. The effects of initial grain size, deformation temperature, strain, and strain rate on the austenitic recrystal-lized volume fraction and grain size were studied using a Gleeble machine. The results show that deformation reduces the grain size when the recrystallized volume fraction is large. The static recrystallized volume fraction increases with increasing deformation temperature, strain, and strain rate, and decreasing initial grain size. The grain size during metadynamic recrystallization is independent of the deformation strain and the initial grain size. The recrystallized volume fraction, the grain size, and the grown grain size calculated by the correlations are consistent with the measured values.

Metadynamic recrystallization and microstructure evolution of a continuously cast Ti-microalloyed steel slab with heavy reduction

The effects of the deformation parameters in the heavy reduction(HR)process on recrystallization kinetics and microstructure evolution were analyzed.Based on the experimental results,metadynamic recrystallization(MDRX)kinetic and austenite grain size models were established for a continuously cast slab during HR.Moreover,the evolution of the quenched microstructure after MDRX was observed using electron backscatter diffraction.The relative frequency of very low-angle grain boundaries decreased from 58.8% to 52.1%,and the relative frequency of high-angle grain boundaries increased from 28.5% to 38.9%.Analyses revealed that the recovery was the main softening mechanism.The decrease in the total grain boundary length indicated that subgrain growth occurred with increasing inter-pass time.The main texture evolved from a {001}<110>texture to a{112}<111>texture,and the texture strength remained unchanged.