Chignolin Simulations

The initial structure of Chignolin was generated starting from the cln025 peptide, with sequence TYR-TYR-ASP-PRO-GLU-THR-GLY-THR-TRP-TYR. The structure was solvated in a cubic box of 40A, containing 1881 water molecules and two Na+ ions to neutralize the peptide's negative charge. MD simulations were performed with ACEMD, using CHARMM22* force field and TIP3P water model at 350K temperature. A Langevin integrator was used with a damping constant of 0.1 1/ps. Integration time step was set to 4 fs, with heavy hydrogen atoms (scaled up to four times the hydrogen mass) and holonomic constrains on all hydrogen-heavy atom bond terms. Electrostatics were computed using Particle Mesh Ewald with a cutoff distance of 9A and grid spacing of 1A. Ten NVT simulations of 1 ns length were carried out, with a dielectric constant of 80 and temperature of 350K to generate ten different starting conformations for the production runs. Production simulations consisted of 3744 independent simulations of 50 ns, for a total aggregate time of 187.2 µs. All simulations were performed using and adaptive sampling algorithm, where multiple rounds of simulations are performed, and each round the available trajectories are analyzed to select the initial coordinates for the next round of simulations. All simulations were run using the GPUGRID distributed computing platform.<br>Chignolin的初始结构源自cln025肽，其氨基酸序列为TYR-TYR-ASP-PRO-GLU-THR-GLY-THR-TRP-TYR。该结构被置于40 Å的立方盒子中进行溶剂化，体系包含1881个水分子与2个Na+离子，以中和该肽链的负电荷。本次模拟采用ACEMD软件开展分子动力学（Molecular Dynamics, MD）模拟，使用CHARMM22*力场与TIP3P水模型，模拟温度设定为350K。模拟采用朗之万（Langevin）积分器，阻尼常数设为0.1 1/ps；积分时间步长设置为4 fs，对经质量缩放的氢原子（将氢原子质量提升至原质量的4倍）以及所有氢-重原子键项施加完整约束。静电相互作用采用粒子网格埃瓦尔德（Particle Mesh Ewald, PME）方法计算，截断距离为9 Å，网格间距为1 Å。我们开展了10组时长为1 ns的NVT恒容恒温系综模拟，介电常数设为80，温度维持350K，以生成10组不同的初始构象，用于后续的生产模拟。生产模拟包含3744组独立的50 ns时长模拟，总累计模拟时长达187.2 µs。所有模拟均采用自适应采样算法完成：即开展多轮模拟循环，每一轮均对当前已获取的轨迹进行分析，以此选取下一轮模拟的初始坐标。所有模拟均运行于GPUGRID分布式计算平台之上。