All atom simulations snapshots and contact maps analysis scripts for SARS-CoV-2002 and SARS-CoV-2 spike proteins with and without ACE2 enzyme
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<strong>The dataset contains a total of 40 snapshots of the four trajectories (10 snapshots each system = two per replica x 5 replicas/system):</strong> SARS-CoV-2002 spike protein without ACE2 SARS-CoV-2 spike protein without ACE2 SARS-CoV-2002 spike protein with ACE2 SARS-CoV-2 spike protein with ACE2 Molecular dynamics simulation trajectories (320ns each) have been performed using the Amber ff14SB force field running with the Amber18 package at the the NSF-funded (OAC-1826915, OAC-1828163) ELSA high performance computing cluster at The College of New Jersey. Under the following simulation methodology: <em>All-atom simulations were carried out with Amber18 (ambermd.org), and system components (protein, ions, water) were modeled with the included FF14SB and TIP3P parameter sets. Energy minimization used CPU pmemd, while later simulation stages used GPU pmemd. CoV2 and CoV1 systems with one RBD up (with/without ACE2) were solvated in 12 angstrom water shells. Cysteine residues identified in the initial models as having a disulfide bond (DB) were bonded using tLeap. All simulations used 0.150 M NaCl. Hydrogen mass repartitioning was applied only to the protein to enable a 4 fs timestep (https://pubs.acs.org/doi/abs/10.1021/ct5010406). The SHAKE algorithm was applied to hydrogens, and a real-space cutoff of 8 angstroms was used. Periodic boundary conditions were applied and PME was used for long-range electrostatics. Minimization was by steepest descent (2000 steps) followed by conjugate gradient (3000 steps). Heating used two stages: (1) NVT heating from 0 K to 100 K (50 ps), and (2) NPT heating from 100 K to 300 K (100 ps). Restraints of 10 kcal mol<sup>-1</sup> angstrom<sup>-2</sup> were applied during minimization and heating to C-alpha atoms. During 6 ns of equilibration at 300 K C-alpha restraints were gradually reduced from 10 kcal mol<sup>-1</sup> angstrom<sup>-2</sup> to 0.1 kcal mol<sup>-1</sup> angstrom<sup>-2</sup>. Finally, restraints were released and 320 ns unrestrained production simulations were carried out for CoV2 and CoV1 systems. Production simulations began from the final equilibrated snapshots, and five copies of each system were simulated. As unrestrained systems can freely rotate we monitored simulations for any close contacts and found that in one copy of the CoV1 simulation without ACE2 and one RBD up that a few contacts close to 8 angstrom occur near the end of the 320 ns between the RBD and a different subdomain of the spike complex in a periodic image. However this did not influence analyzed structural properties which is verified by comparing results across simulations. The Monte Carlo barostat was used to maintain pressure (1 atm), and the Langevin thermostat was used to maintain 300 K temperature (collision frequency 1 ps<sup>-1</sup>), as implemented in Amber18. In aggregate, nearly 7 microseconds of simulation of systems ranging from 396,147 to 879,100 atoms was carried out for this work.</em><br> For further details on the trajectories, please contact Joseph Baker (bakerj@tcnj.edu). <strong>Regarding the contact map analysis scripts (contactMaps_Analysis.tar.gz), they contain the following workflow:</strong> contactmap --> source files from contact_map executable<br> process_nc.sh --> convert raw data from all-atom simulation to numbered PDB files and get the contact maps<br> frequency.lua --> read a set of PDB files and output the frequency count for each contact<br> consensus.fasta --> align sequence of Covid19 and SARS from Chimera<br> consensus.lua --> read data previously generated and compute the frequency per residue, among other things.<br> consensus.sh --> input information to consensus.lua<br> consensus.gp --> gnuplot script to plot figures This dataset and the code is part of tripartite collaboration between: The Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland (supported by the National Science Centre, Poland, under grant No. 2017/26/D/NZ1/0046) Department of Chemistry, The College of New Jersey, New Jersey, United States (supported by National Science Foundation under grant numbers OAC-1826915 and OAC-1828163). Jozef Stefan Institute, Ljubljana, Slovenia (supported by the Slovenian Research Agency (Funding No. P1-0055)).
本数据集共包含4类轨迹的40个快照（每个体系10个快照=每个重复2个快照×5个重复体系），四类轨迹分别为：无ACE2的SARS-CoV-2002刺突蛋白、无ACE2的SARS-CoV-2刺突蛋白、结合ACE2的SARS-CoV-2002刺突蛋白、结合ACE2的SARS-CoV-2刺突蛋白。 所有轨迹均采用Amber18软件包（ambermd.org）结合Amber ff14SB力场完成分子动力学模拟，单条轨迹时长为320ns，计算运行于新泽西学院（The College of New Jersey）的ELSA高性能计算集群，该集群由美国国家科学基金会（NSF）资助，资助编号为OAC-1826915、OAC-1828163。 详细模拟方法如下： 采用全原子模拟方案，模拟体系包含蛋白质、离子、溶剂水，分别使用内置的FF14SB力场与TIP3P参数集进行建模。能量最小化步骤使用CPU版本的pmemd模块，后续模拟阶段则采用GPU加速的pmemd模块。对于受体结合域（Receptor Binding Domain, RBD）向上的CoV2与CoV1体系（结合/未结合ACE2），采用12埃的水壳层进行溶剂化。初始模型中被鉴定为形成二硫键（disulfide bond, DB）的半胱氨酸残基，通过tLeap工具完成成键。所有模拟体系均使用0.150 M的NaCl溶液。仅对蛋白质应用氢质量重分块技术，以支持4 fs的积分步长（参考文献：https://pubs.acs.org/doi/abs/10.1021/ct5010406）。采用SHAKE算法约束氢原子运动，实空间截断半径设置为8埃，使用周期性边界条件，并通过粒子网格埃wald（Particle Mesh Ewald, PME）方法处理长程静电相互作用。 能量最小化先采用最速下降法（2000步），随后采用共轭梯度法（3000步）。升温过程分为两个阶段：(1) NVT系综下从0 K升温至100 K，时长50 ps；(2) NPT系综下从100 K升温至300 K，时长100 ps。在能量最小化与升温阶段，对Cα原子施加10 kcal·mol⁻¹·Å⁻²的位置约束。在300 K下进行6 ns的平衡模拟期间，Cα原子的位置约束从10 kcal·mol⁻¹·Å⁻²逐步降低至0.1 kcal·mol⁻¹·Å⁻²。最终移除所有约束，对CoV2与CoV1体系开展320 ns的无约束生产模拟。生产模拟均从平衡阶段的最终快照起始，每个体系设置5个重复模拟。由于无约束体系可自由旋转，我们对模拟过程中的近距离接触进行了监测，发现在1个未结合ACE2且RBD向上的CoV1模拟重复中，模拟末期在周期性镜像体系内，RBD与刺突复合物的另一亚基之间出现了接近8埃的少量接触。但该现象并未影响后续分析的结构性质，这一点通过对比不同重复模拟的结果得到了验证。模拟过程中采用蒙特卡洛（Monte Carlo）恒压器维持体系压力为1 atm，使用朗之万（Langevin）恒温器维持体系温度为300 K，碰撞频率设置为1 ps⁻¹，上述设置均基于Amber18软件的内置实现。本研究累计完成了原子数介于396147至879100之间的多个体系的模拟，总模拟时长近7微秒。 若需获取轨迹的更多细节，请联系Joseph Baker（邮箱：bakerj@tcnj.edu）。关于接触图谱分析脚本（contactMaps_Analysis.tar.gz），其包含如下工作流程： 1. contactmap：调用contact_map可执行文件的源文件 2. process_nc.sh：将全原子模拟的原始数据转换为带有序号的PDB文件，并生成接触图谱 3. frequency.lua：读取一组PDB文件，输出每一对接触的频率统计结果 4. consensus.fasta：通过Chimera工具比对SARS-CoV-2与SARS的序列 5. consensus.lua：读取此前生成的结果，计算每残基的频率等统计信息 6. consensus.sh：为consensus.lua提供输入信息 7. consensus.gp：用于绘制图表的Gnuplot脚本 本数据集与配套代码来自三方合作项目，合作单位分别为： 1. 波兰科学院基础技术研究所，波兰华沙（受波兰国家科学中心资助，项目编号2017/26/D/NZ1/0046） 2. 新泽西学院化学系，美国新泽西州（受美国国家科学基金会资助，项目编号OAC-1826915与OAC-1828163） 3. 约瑟夫·斯特凡研究所，斯洛文尼亚卢布尔雅那（受斯洛文尼亚研究机构资助，资助编号P1-0055）
