Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301;
Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301;Instituto de Matemática Aplicada San Luis, Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Universidad Nacional de San Luis, 5700 San Luis, Argentina; and.
Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8458-63. doi: 10.1073/pnas.1407837111. Epub 2014 May 27.
By using local (free-energy profiles along the amino acid sequence and (13)C(α) chemical shifts) and global (principal component) analyses to examine the molecular dynamics of protein-folding trajectories, generated with the coarse-grained united-residue force field, for the B domain of staphylococcal protein A, we are able to (i) provide the main reason for formation of the mirror-image conformation of this protein, namely, a slow formation of the second loop and part of the third helix (Asp29-Asn35), caused by the presence of multiple local conformational states in this portion of the protein; (ii) show that formation of the mirror-image topology is a subtle effect resulting from local interactions; (iii) provide a mechanism for how protein A overcomes the barrier between the metastable mirror-image state and the native state; and (iv) offer a plausible reason to explain why protein A does not remain in the metastable mirror-image state even though the mirror-image and native conformations are at least energetically compatible.
通过使用局部（沿氨基酸序列的自由能分布和（13）C（α）化学位移）和全局（主成分）分析来研究由粗粒度联合残基力场生成的葡萄球菌蛋白 A 的 B 结构域的蛋白质折叠轨迹的分子动力学，我们能够：（i）提供形成该蛋白质镜像构象的主要原因，即第二个环和部分第三个螺旋（Asp29-Asn35）的形成缓慢，这是由于该蛋白质部分存在多个局部构象状态；（ii）表明镜像拓扑的形成是局部相互作用的微妙影响；（iii）提供了一种机制，说明蛋白 A 如何克服亚稳镜像状态和天然状态之间的障碍；（iv）提供了一个合理的解释，说明为什么蛋白 A 即使镜像构象和天然构象在能量上至少是兼容的，也不会停留在亚稳镜像状态。
