Brooks B, Karplus M
Proc Natl Acad Sci U S A. 1983 Nov;80(21):6571-5. doi: 10.1073/pnas.80.21.6571.
A normal mode analysis making use of an empirical potential function including local and nonlocal (nonbonded) interactions is performed for the bovine pancreatic trypsin inhibitor in the full conformational space of the molecule (1,740 degrees of freedom); that is, all bond lengths and angles, as well as dihedral angles, are included for the 580-atom system consisting of all heavy atoms and polar hydrogens. The heavy-atom frequency spectrum shows a dense distribution between 3 and 1,800 cm-1, with 350 modes below 216 cm-1. Most of the low-frequency modes, of which many have significant anharmonic character, are found to be delocalized over the protein. The root-mean-square amplitudes of the atomic fluctuations are calculated at 300 K from the normal modes and compared with those obtained from a solution molecular dynamics simulation based on the same potential function; very good agreement is obtained for the variation in the main-chain fluctuations as a function of residue number, though larger differences occur for the side chains. The fluctuations are generally, though not always, dominated by frequencies below 30 cm-1, in accord with the results of the dynamics simulation. The vibrational contributions to the thermodynamic properties of the protein are calculated as a function of temperature; the effects of perturbations on the spectrum, suggested for ligand or substrate binding, are examined. The analysis demonstrates that, in spite of the anharmonic contributions to the potential, a normal mode description can provide useful results concerning the internal motions of proteins.
利用包含局部和非局部（非键合）相互作用的经验势函数，对牛胰蛋白酶抑制剂在分子的全构象空间（1740个自由度）中进行了正常模式分析；也就是说，对于由所有重原子和极性氢组成的580原子系统，考虑了所有键长、键角以及二面角。重原子频谱在3至1800 cm-1之间呈现密集分布，在216 cm-1以下有350种模式。发现大多数低频模式，其中许多具有显著的非谐特性，在蛋白质上是离域的。根据正常模式计算了300 K时原子涨落的均方根振幅，并与基于相同势函数的溶液分子动力学模拟得到的结果进行比较；尽管侧链存在较大差异，但主链涨落随残基编号的变化得到了很好的一致性。与动力学模拟结果一致，涨落通常（但并非总是）由低于30 cm-1的频率主导。计算了振动对蛋白质热力学性质的贡献随温度的变化；研究了配体或底物结合对光谱扰动的影响。分析表明，尽管势函数存在非谐贡献，但正常模式描述可以提供有关蛋白质内部运动的有用结果。
