Friedel Miriam, Baumketner Andrij, Shea Joan-Emma
Department of Physics, University of California, Santa Barbara, California 93106, USA.
J Chem Phys. 2007 Mar 7;126(9):095101. doi: 10.1063/1.2464114.
Surface-tethered proteins are increasingly being used in a variety of experimental situations, and they are the basis for many new technologies. Nevertheless, a thorough understanding of how a surface can impact the native state stability of an attached protein is lacking. In this work, the authors use molecular dynamics simulations of a model beta-barrel protein to investigate how surface tethering influences native state stability. They find that stability, as measured by the folding temperature Tf, can be either increased, decreased, or remain unchanged as a result of tethering. Observed shifts are highly dependent on the location of residue used as the tether point, and stability is influenced by a number of factors, both energetic and entropic. These factors include native state vibrations, loss of bulk unfolded conformations, changes to the unfolded state ensemble, and the emergence of an entropic term not present for the bulk protein. They discuss each of these contributions in detail and comment on their relative importance and connection to experiment.
表面 tethered 蛋白越来越多地用于各种实验情况，并且它们是许多新技术的基础。然而，目前缺乏对表面如何影响附着蛋白的天然态稳定性的全面理解。在这项工作中，作者使用模型β-桶蛋白的分子动力学模拟来研究表面 tethering 如何影响天然态稳定性。他们发现，通过折叠温度 Tf 测量的稳定性，可能会因 tethering 而增加、降低或保持不变。观察到的变化高度依赖于用作 tether 点的残基的位置，并且稳定性受到许多因素的影响，包括能量和熵。这些因素包括天然态振动、大量未折叠构象的丧失、未折叠态系综的变化以及大量蛋白不存在的熵项的出现。他们详细讨论了这些贡献中的每一个，并对它们的相对重要性以及与实验的联系进行了评论。
