All-atom molecular dynamics simulation of peptides

The initial structure was built using the LEaP module of AmberTools21, and we will run a total of 4000 minimization steps before starting to run molecular dynamics; 2000 is the steepest decline, followed by the conjugate gradient of 2000. That should be enough to clean up our structures. Then heat and equilibrate in three 250 ps stages: from heat 100 K to production temperature 300K, heavy atom position limiting, force constant decreasing from 10.0 to 1.0, then decreasing to 0.1 kcal/mol/Ų. The step size was set to 0.002 and the unconstrained production simulation was performed in an implicit generalized Bonn solvent (igb=8) in the canonical ensemble (NVT). The temperature was controlled by a Langevin thermostat (ntt=3) and molecular dynamics was performed for 200ns at a collision frequency of γ= 0.01 ps^-1(For implicit solvent, setting collision frequency to 0.01ps⁻¹ can lead to significant, up to 100-fold in some cases, speedup of conformational sampling). Finally, the cpptraj module of AmberTools21 was used for combined clustering, RMSD, and other molecular dynamics trajectory analysis.

本研究的初始结构通过AmberTools21的LEaP模块构建完成。我们将在启动分子动力学模拟前，总计执行4000步能量最小化操作：前2000步采用最陡下降法，后2000步采用共轭梯度法，该操作足以优化体系结构以消除不合理的空间排布。随后分三个250 ps的阶段完成升温和体系平衡：将体系从100 K加热至生产模拟目标温度300 K，过程中施加重原子位置约束，力常数从10.0 kcal/mol/Ų逐步降至1.0，随后再降至0.1 kcal/mol/Ų。模拟步长设置为0.002，随后在隐式广义玻恩溶剂模型（igb=8）的正则系综（NVT）下开展无约束生产模拟。体系温度通过朗之万恒温器（Langevin thermostat，ntt=3）进行调控，模拟总时长为200 ns，碰撞频率γ设置为0.01 ps⁻¹。对于隐式溶剂体系，将碰撞频率设为0.01 ps⁻¹可显著加速构象采样，部分场景下加速幅度可达100倍。最终通过AmberTools21的cpptraj模块完成聚类、均方根偏差（RMSD）等分子动力学轨迹分析工作。