Bahar I, Wallqvist A, Covell D G, Jernigan R L
Molecular Structure Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-5677, USA.
Biochemistry. 1998 Jan 27;37(4):1067-75. doi: 10.1021/bi9720641.
Recently, we developed a simple analytical model based on local residue packing densities and the distribution of tertiary contacts for describing the conformational fluctuations of proteins in their folded state. This so-called Gaussian network model (GNM) is applied here to the interpretation of experimental hydrogen exchange (HX) behavior of proteins in their native state or under weakly denaturing conditions. Calculations are performed for five proteins: bovine pancreatic trypsin inhibitor, cytochrome c, plastocyanin, staphylococcal nuclease, and ribonuclease H. The results are significant in two respects. First, a good agreement is reached between calculated fluctuations and experimental measurements of HX despite the simplicity of the model and within computational times 2 or 3 orders of magnitude faster than earlier, more complex simulations. Second, the success of a theory, based on the coupled conformational fluctuations of residues near the native state, to satisfactorily describe the native-state HX behavior indicates the significant contribution of local, but cooperative, fluctuations to protein conformational dynamics. The correlation between the HX data and the unfolding kinetics of individual residues further suggests that local conformational susceptibilities as revealed by the GNM approach may have implications relevant to the global dynamics of proteins.
最近，我们基于局部残基堆积密度和三级接触分布开发了一个简单的分析模型，用于描述蛋白质折叠状态下的构象波动。这个所谓的高斯网络模型（GNM）在此处用于解释蛋白质在天然状态或弱变性条件下的实验氢交换（HX）行为。对五种蛋白质进行了计算：牛胰蛋白酶抑制剂、细胞色素c、质体蓝素、葡萄球菌核酸酶和核糖核酸酶H。结果在两个方面具有重要意义。首先，尽管模型简单，但计算得到的波动与HX的实验测量结果之间达成了良好的一致性，且计算时间比早期更复杂的模拟快2到3个数量级。其次，基于天然状态附近残基的耦合构象波动的理论能够成功地令人满意地描述天然状态下的HX行为，这表明局部但协同的波动对蛋白质构象动力学有重大贡献。HX数据与单个残基的解折叠动力学之间的相关性进一步表明，GNM方法揭示的局部构象敏感性可能与蛋白质的整体动力学相关。
