Kmiecik Sebastian, Kolinski Andrzej
Faculty of Chemistry, University of Warsaw, L. Pasteura 1, 02-093 Warsaw, Poland.
Biophys J. 2008 Feb 1;94(3):726-36. doi: 10.1529/biophysj.107.116095. Epub 2007 Sep 21.
The understanding of the folding mechanisms of single-domain proteins is an essential step in the understanding of protein folding in general. Recently, we developed a mesoscopic CA-CB side-chain protein model, which was successfully applied in protein structure prediction, studies of protein thermodynamics, and modeling of protein complexes. In this research, this model is employed in a detailed characterization of the folding process of a simple globular protein, the B1 domain of IgG-binding protein G (GB1). There is a vast body of experimental facts and theoretical findings for this protein. Performing unbiased, ab initio simulations, we demonstrated that the GB1 folding proceeds via the formation of an extended folding nucleus, followed by slow structure fine-tuning. Remarkably, a subset of native interactions drives the folding from the very beginning. The emerging comprehensive picture of GB1 folding perfectly matches and extends the previous experimental and theoretical studies.
理解单结构域蛋白质的折叠机制是全面理解蛋白质折叠的关键一步。最近，我们开发了一种介观CA-CB侧链蛋白质模型，该模型已成功应用于蛋白质结构预测、蛋白质热力学研究以及蛋白质复合物建模。在本研究中，该模型用于详细表征一种简单球状蛋白质——免疫球蛋白结合蛋白G（GB1）的B1结构域的折叠过程。关于这种蛋白质，有大量的实验事实和理论发现。通过进行无偏的从头算模拟，我们证明GB1的折叠过程是通过形成一个伸展的折叠核，随后进行缓慢的结构微调。值得注意的是，一部分天然相互作用从一开始就驱动着折叠过程。由此呈现的GB1折叠的全面图景与先前的实验和理论研究完美匹配并加以拓展。
