Voltz Karine, Trylska Joanna, Tozzini Valentina, Kurkal-Siebert Vandana, Langowski Jörg, Smith Jeremy
Biophysics of Macromolecules, German Cancer Research Center, Heidelberg, Germany.
J Comput Chem. 2008 Jul 15;29(9):1429-39. doi: 10.1002/jcc.20902.
A coarse-grained simulation model for the nucleosome is developed, using a methodology modified from previous work on the ribosome. Protein residues and DNA nucleotides are represented as beads, interacting through harmonic (for neighboring) or Morse (for nonbonded) potentials. Force-field parameters were estimated by Boltzmann inversion of the corresponding radial distribution functions obtained from a 5-ns all-atom molecular dynamics (MD) simulation, and were refined to produce agreement with the all-atom MD simulation. This self-consistent multiscale approach yields a coarse-grained model that is capable of reproducing equilibrium structural properties calculated from a 50-ns all-atom MD simulation. This coarse-grained model speeds up nucleosome simulations by a factor of 10(3) and is expected to be useful in examining biologically relevant dynamical nucleosome phenomena on the microsecond timescale and beyond.
我们开发了一种用于核小体的粗粒度模拟模型，采用了一种对先前核糖体研究工作进行修改的方法。蛋白质残基和DNA核苷酸被表示为珠子，通过谐势（用于相邻珠子）或莫尔斯势（用于非键合珠子）相互作用。力场参数通过对从5纳秒全原子分子动力学（MD）模拟获得的相应径向分布函数进行玻尔兹曼反演来估计，并进行了优化以使其与全原子MD模拟结果相符。这种自洽的多尺度方法产生了一个粗粒度模型，该模型能够重现从50纳秒全原子MD模拟计算得到的平衡结构性质。这个粗粒度模型将核小体模拟速度提高了10³倍，预计在研究微秒及更长时间尺度上与生物学相关的动态核小体现象方面将很有用。
