Moritsugu Kei, Kurkal-Siebert Vandana, Smith Jeremy C
Center for Molecular Biophysics, University of Tennessee/Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA.
Biophys J. 2009 Aug 19;97(4):1158-67. doi: 10.1016/j.bpj.2009.05.015.
The REACH (realistic extension algorithm via covariance Hessian) coarse-grained biomolecular simulation method is a self-consistent multiscale approach directly mapping atomistic molecular dynamics simulation results onto a residue-scale model. Here, REACH is applied to calculate the dynamics of protein-protein interactions. The intra- and intermolecular fluctuations and the intermolecular vibrational densities of states derived from atomistic molecular dynamics are well reproduced by the REACH normal modes. The phonon dispersion relations derived from the REACH lattice dynamics model of crystalline ribonuclease A are also in satisfactory agreement with the corresponding all-atom results. The REACH model demonstrates that increasing dimer interaction strength decreases the translational and rotational intermolecular vibrational amplitudes, while their vibrational frequencies are relatively unaffected. A comparative study of functionally interacting biological dimers with crystal dimers, which are formed artificially via crystallization, reveals a relation between their static structures and the interprotein dynamics: i.e., the consequence of the extensive interfaces of biological dimers is reduction of the intermonomer translational and rotational amplitudes, but not the frequencies.
REACH（通过协方差海森矩阵的现实扩展算法）粗粒度生物分子模拟方法是一种自洽的多尺度方法，可将原子分子动力学模拟结果直接映射到残基尺度模型上。在此，应用REACH来计算蛋白质-蛋白质相互作用的动力学。REACH正则模式很好地再现了源自原子分子动力学的分子内和分子间波动以及分子间振动态密度。从结晶核糖核酸酶A的REACH晶格动力学模型导出的声子色散关系也与相应的全原子结果令人满意地一致。REACH模型表明，增加二聚体相互作用强度会降低分子间平移和旋转振动幅度，而它们的振动频率相对不受影响。对通过结晶人工形成的功能相互作用生物二聚体与晶体二聚体的比较研究揭示了它们的静态结构与蛋白间动力学之间的关系：即生物二聚体广泛界面的结果是单体间平移和旋转幅度的降低，而非频率的降低。
