Dobson Neil, Dantas Gautam, Baker David, Varani Gabriele
Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.
Structure. 2006 May;14(5):847-56. doi: 10.1016/j.str.2006.02.011.
Achieving atomic-level resolution in the computational design of a protein structure remains a challenging problem despite recent progress. Rigorous experimental tests are needed to improve protein design algorithms, yet studies of the structure and dynamics of computationally designed proteins are very few. The NMR structure and backbone dynamics of a redesigned protein of 96 amino acids are compared here with the design target, human U1A protein. We demonstrate that the redesigned protein reproduces the target structure to within the uncertainty of the NMR coordinates, even as 65 out of 96 amino acids were simultaneously changed by purely computational methods. The dynamics of the backbone of the redesigned protein also mirror those of human U1A, suggesting that the protein design algorithm captures the shape of the potential energy landscape in addition to the local energy minimum.
尽管最近取得了进展，但在蛋白质结构的计算设计中实现原子级分辨率仍然是一个具有挑战性的问题。需要严格的实验测试来改进蛋白质设计算法，然而对计算设计蛋白质的结构和动力学的研究却非常少。本文将一种重新设计的96个氨基酸的蛋白质的核磁共振结构和主链动力学与设计目标——人类U1A蛋白进行了比较。我们证明，即使96个氨基酸中的65个通过纯计算方法同时发生了改变，重新设计的蛋白质仍能在核磁共振坐标的不确定性范围内重现目标结构。重新设计的蛋白质主链的动力学也反映了人类U1A蛋白的动力学，这表明蛋白质设计算法除了能捕捉局部能量最小值外，还能捕捉势能面的形状。
