中文摘要：

残基突变是提高蛋白质热稳定性最直接有效的方式。在本文中,我们选取一对冷休克蛋白质作为研究对象,其中一个来自嗜温的Bacillus subtilis（Bs-CspB）,另一个来自嗜热的Bacillus caldolyticus（Bc-Csp）,这两个蛋白质在序列和结构上具有高度的相似性,但两者的耐热能力却相差很大。我们利用全原子模型计算残基突变前后蛋白质的自由能和氨基酸之间相互作用能的变化,分析残基突变对冷休克蛋白热稳定性的影响。通过对比两个蛋白质对应位置上残基的能量,我们成功鉴别出对Bc-Csp的高热稳定性有突出贡献的残基。我们计算了这些残基突变前后,该残基的静电相互作用和范德华相互作用的变化,以分析该残基对Bc-Csp高热稳定性的主要贡献。同时,我们分析了离子键对蛋白质热稳定性的贡献。我们的计算结果和实验结果吻合得很好,关键在于利用该方法可以详细地说明残基突变影响蛋白质热稳定性的根本原因。本文为研究残基突变对蛋白质热稳定性的影响提供了一种计算思路和方法,并有助于设计具有高耐热能力的蛋白质。

英文摘要：

Residue mutation is an effective and direct way to improve protein thermostability.In this paper we analyzed the effects of residue mutations on thermostability of a pair of cold shock proteins,mesophile Bacillus subtilis（Bs-CspB） and its thermophilic counterpart Bacillus caldolyticus（Bc-Csp） by calculating the global free energies,residue-residue interactions and their changes after residue mutations.By comparing the free energy differences of residues at the same position of Bs-CspB and Bc-Csp,we successfully identified those residues that contribute greatly to the increased thermostability of Bc-Csp.We also analyzed the relative contributions of electrostatic and Van der Waals（VdW） interactions of these mutations to the thermostability of Bc-Csp.The possible role of ion bonds to thermostability was also discussed.Our results are in good agreement with the experiments but give more details about how residue mutations affect the thermostability of Bc-Csp.Our method provides a computational way to predict the effects of residue mutations on protein thermostability and may be helpful to the design of proteins with higher thermostability.