State-of-the-Art Molecular Dynamics Simulation Studies of RNA-Dependent RNA Polymerase of SARS-CoV-2

Molecular dynamics (MD) simulations are powerful theoretical methods that can reveal biomolecular properties, such as structure, fluctuations, and ligand binding, at the level of atomic detail. In this review article, recent MD simulation studies on these biomolecular properties of the RNA-dependent RNA polymerase (RdRp), which is a multidomain protein, of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are presented. Although the tertiary structures of RdRps in SARS-CoV-2 and SARS-CoV are almost identical, the RNA synthesis activity of RdRp of SARS-CoV is higher than SARS-CoV-2. Recent MD simulations observed a difference in the dynamic properties of the two RdRps, which may cause activity differences. RdRp is also a drug target for Coronavirus disease 2019 (COVID-19). Nucleotide analogs, such as remdesivir and favipiravir, are considered to be taken up by RdRp and inhibit RNA replication. Recent MD simulations revealed the recognition mechanism of RdRp for these drug molecules and adenosine triphosphate (ATP). The ligand-recognition ability of RdRp decreases in the order of remdesivir, favipiravir, and ATP. As a typical recognition process, it was found that several lysine residues of RdRp transfer these ligand molecules to the binding site such as a “bucket brigade.” This finding will contribute to understanding the mechanism of the efficient ligand recognition by RdRp. In addition, various simulation studies on the complexes of SARS-CoV-2 RdRp with several nucleotide analogs are reviewed, and the molecular mechanisms by which these compounds inhibit the function of RdRp are discussed. The simulation studies presented in this review will provide useful insights into how nucleotide analogs are recognized by RdRp and inhibit the RNA replication.     

Function-Related Asymmetry of the Interactions between Matrix Loops and Conserved Sequence Motifs in the Mitochondrial ADP/ATP Carrier

The ADP/ATP carrier (AAC) plays a central role in oxidative metabolism by exchanging ATP and ADP across the inner mitochondrial membrane. Previous experiments have shown the involvement of the matrix loops of AAC in its function, yet potential mechanisms remain largely elusive. One obstacle is the limited information on the structural dynamics of the matrix loops. In the current work, unbiased all-atom molecular dynamics (MD) simulations were carried out on c-state wild-type AAC and mutants. Our results reveal that: (1) two ends of a matrix loop are tethered through interactions between the residue of triplet 38 (Q38, D143 and Q240) located at the C-end of the odd-numbered helix and residues of the [YF]xG motif located before the N-end of the short matrix helix in the same domain; (2) the initial progression direction of a matrix loop is determined by interactions between the negatively charged residue of the [DE]G motif located at the C-end of the short matrix helix and the capping arginine (R30, R139 and R236) in the previous domain; (3) the two chemically similar residues D and E in the highly conserved [DE]G motif are actually quite different; (4) the N-end of the M3 loop is clamped by the [DE]G motif and the capping arginine of domain 2 from the two sides, which strengthens interactions between domain 2 and domain 3; and (5) a highly asymmetric stable core exists within domains 2 and 3 at the m-gate level. Moreover, our results help explain almost all extremely conserved residues within the matrix loops of the ADP/ATP carriers from a structural point of view. Taken together, the current work highlights asymmetry in the three matrix loops and implies a close relationship between asymmetry and ADP/ATP transport.     

超长综采工作面撤架期间煤自燃预测及防控技术研究

大兴煤矿北一202工作面采用超长开切眼布置,存在采空区空间大、开采易自燃煤层、工作面全程俯采且顶板存在复合煤岩层采空区遗煤量大等因素,导致工作面防灭火工作难度大幅提高。通过在工作面进、回风巷道,以及上、下隅角向工作面70 m处架后采空区预埋4个束管测点,对北一202超长俯采工作面采空区自燃“三带”分布范围进行多点位观测,得出超长俯采工作面采空区最大氧化带宽度为37.7 m,位于上隅角向工作面70 m架后采空区。根据北一202工作面实际参数,建立三维几何模型,通过Fluent数值模拟分析,揭示了超长俯采工作面采空区流场及O₂体积分数变化规律,并将采空区自燃“三带”分布范围模拟结果与实测结果进行对比,发现两者基本一致,证明了采用数值模拟方法分析研究超长俯采工作面采空区流场、O₂体积分数分布规律的有效性和科学性。

     

深凹露天矿采场内流场分布规律的试验与数值模拟

为探究大气风速对深凹露天矿山爆破排烟时间的影响,采用CFD数值模拟方法构建了深凹露天矿山爆破非稳态数值模型,模拟大气风速为3、6、9、15 m/s和不同爆破位置条件下炮烟扩散场景,研究了不同大气风速对深凹露天采坑内风流场特征和爆破排烟时间的影响。研究结果表明：不同爆破位置下,随着大气风速的增大,露天采坑内的风流分布呈现出单复环流向双复环流结构的转变;当大气风速大于6 m/s后,随着大气风速的增大,爆破炮烟排烟时间下降的幅度逐渐减小,大气风速对排烟时间的影响逐渐降低;不同爆破位置下,随着大气风速的增大,露天采坑爆破炮烟排烟时间均呈现下降趋势,且与大气风速呈现良好的指数函数关系。

     

涡流管热冷出口压力比对其性能的影响研究

采用Fluent数值模拟的方法,以R41、R23、R32、R290、R1234yf、R134a为工质对涡流管进行三维数值模拟,得出不同工质涡流管制冷效应、制热效应以及分离效应随热冷出口压力比的变化规律,并以R41为工质分析不同流道数目涡流管性能随热冷出口压力比的变化规律。模拟结果表明:R41的制冷、制热以及分离效应最好,最大分离效应可达5 K左右;不同工质涡流管制热效应以及分离效应随热冷出口压力比的增大而增大,制冷效应随热冷出口压力比的增大而减小;不同热冷出口压力比条件下,随着喷嘴流道数的增加涡流管制冷效应逐渐降低而制热效应逐渐升高。     

强流脉冲电子束表面改性镍基合金的研究

DZ22合金因其优良的高温性能被广泛的应用于高温热端构件。为了进一步提高DZ22合金表面性能,使用强流脉冲电子束对其表面进行轰击。本文主要讨论温度场模拟及微观组织状态。采用abaqus模拟软件对轰击时DZ22镍基合金表面的温度场进行模拟。模拟结果表明,轰击时试样表面在0.68μs时达到轰击时表面的最高温度1629℃,超过DZ22镍基高温合金熔点。利用激光共聚焦显微镜对轰击前后合金表面形貌进行观测,实验结果显示,轰击后试样表面产生熔坑形貌。利用X射线衍射仪对轰击前后合金表面组织结构进行分析,实验表明,轰击使合金表面应力状态与晶粒的生长方向发生改变。结果表明,轰击使得DZ22合金表面出现熔坑形貌且改变其晶粒方向。     

复合振冲碎石桩加固机理及施工过程数值模拟

采用振动荷载作用下超孔隙水压力产生的能量模型,考虑耗散能量和孔径扩张的影响及相互作用,并进行合理的简化,对复合振冲碎石桩施工过程做了数值模拟.采用有限差分离散求解复合振冲碎石桩边值问题,编制相应的数值程序,基于模拟结果详细讨论了排水井的存在对复合振冲碎石桩孔隙水压力发展变化的影响.最后对普通碎石桩和复合碎石桩的地基加固效果进行对比分析.数值模拟结果表明,复合振冲碎石桩由于排水井的存在,使地基加固范围明显增大,并且可以应用于渗透系数较小的粉土和砂质粉土地基中.     

激光冲击强化设备控制系统

针对复杂曲面类零件,研发一种新型表面激光冲击强化的控制系统,该系统是一套全自动可控操作系统,通过工控机/PLC集成控制,实现自动化、数字化控制,并完成实时在线监控和信息交互反馈,属于开放式分布系统。该系统用于激光冲击强化核心设备(包括激光器、机器人、辅助控制、质量检测装置与辅助系统等),实现各环节的信息交互和系统的协同工作,通过实时监控系统,远程观察加工状态,有效避免重大事故的发生。同时,该控制系统添加激光冲击强化工艺试验数据记录功能,可根据实际需求调用后台工艺参数数据库,实现高效工艺参数优化。除此之外,该系统还能够实现激光冲击强化模型建立、加工过程有限元模拟、复杂曲面加工轨迹自动规划、加工策略制定等功能,从而实现激光冲击强化自动化生产,目前已经处于工程应用阶段。     

桩端岩溶顶板的破坏特征试验与理论计算模型研究

基于分离相似设计方法,开展了顶板厚度和溶洞直径变化下桩端顶板的破坏特征模型试验,并构建了相应的安全厚度理论计算模型。1)溶洞顶板厚度的大小影响了桩基嵌岩端荷载的传递路径,厚度越大传递范围越广,形成的剪切带体积越大。顶板厚度t≤1.0d时(d为桩径)顶板临空面处易发生冲切破坏,此时溶洞顶板的自身稳定性起控制作用,顶板厚度越小,溶洞临空面处脱落体积越小;顶板厚度1.0d< t ≤2.0d时,表现为锥形冲切失稳驱动上部剪切错动的破坏;顶板厚度t >2.0d时,表现为上部剪切错动驱动临空面的锥形冲切失稳,且溶洞直径小于剪切错动体的横向宽度时,剪切破坏最终发生在桩-岩界面的竖向投影范围以内。顶板厚度较小,对应的Q-S曲线为典型的陡降型曲线,而厚度较大时Q-S曲线为典型的缓变型。2)顶板具有一定厚度情况下(t≥2.0d),洞径较小(l≤3.0d)时,桩端剪切变形较为显著,上部剪切错动达到一定程度后,顶板临空面才发生冲切破坏,此时Q-S曲线呈现缓变型趋势;洞径较大时(l >3.0d),顶板临空面处冲切现象较显著,且洞径越大锥形冲切块的体积越大,此时Q-S曲线呈陡降型变化特征。3)以锥形冲切破坏计算模型进行工程设计风险较大,而冲-剪破坏理论模型与顶板岩体强度、完整性、桩径、嵌岩深度、施工方法及工艺等相关,故现场条件下即可计算出顶板的最小安全厚度值。