Schell David, Tsai Jerry, Scholtz J Martin, Pace C Nick
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.
Proteins. 2006 May 1;63(2):278-82. doi: 10.1002/prot.20826.
The contribution of hydrogen bonds and the burial of polar groups to protein stability is a controversial subject. Theoretical studies suggest that burying polar groups in the protein interior makes an unfavorable contribution to the stability, but experimental studies show that burying polar groups, especially those that are hydrogen bonded, contributes favorably to protein stability. Understanding the factors that are not properly accounted for by the theoretical models would improve the models so that they more accurately describe experimental results. It has been suggested that hydrogen bonds may contribute to protein stability, in part, by increasing packing density in the protein interior, and thereby increasing the contribution of van der Waals interactions to protein stability. To investigate the influence of hydrogen bonds on packing density, we analyzed 687 crystal structures and determined the volume of buried polar groups as a function of their extent of hydrogen bonding. Our findings show that peptide groups and polar side chains that form hydrogen bonds occupy a smaller volume than the same groups when they do not form hydrogen bonds. For example, peptide groups in which both polar groups are hydrogen bonded occupy a volume, on average, 5.2 A3 less than a peptide group that is not hydrogen bonded.
氢键以及极性基团的埋藏对蛋白质稳定性的贡献是一个存在争议的话题。理论研究表明，将极性基团埋藏在蛋白质内部对稳定性产生不利影响，但实验研究表明，埋藏极性基团，尤其是那些形成氢键的极性基团，对蛋白质稳定性有有利贡献。了解理论模型未恰当考虑的因素将改进这些模型，使其能更准确地描述实验结果。有人提出，氢键可能部分通过增加蛋白质内部的堆积密度，从而增加范德华相互作用对蛋白质稳定性的贡献，来对蛋白质稳定性产生影响。为了研究氢键对堆积密度的影响，我们分析了687个晶体结构，并确定了埋藏极性基团的体积与其氢键形成程度的函数关系。我们的研究结果表明，形成氢键的肽基团和极性侧链比不形成氢键时占据更小的体积。例如，两个极性基团都形成氢键的肽基团平均比未形成氢键的肽基团少占据5.2 ų的体积。
