Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA.
J Am Chem Soc. 2011 Mar 30;133(12):4190-2. doi: 10.1021/ja110296z. Epub 2011 Mar 9.
The de novo design of protein-binding peptides is challenging because it requires the identification of both a sequence and a backbone conformation favorable for binding. We used a computational strategy that iterates between structure and sequence optimization to redesign the C-terminal portion of the RGS14 GoLoco motif peptide so that it adopts a new conformation when bound to Gα(i1). An X-ray crystal structure of the redesigned complex closely matches the computational model, with a backbone root-mean-square deviation of 1.1 Å.
从头设计与蛋白质结合的肽是具有挑战性的,因为它需要确定有利于结合的序列和骨架构象。我们使用了一种在结构和序列优化之间反复迭代的计算策略,重新设计了 RGS14 GoLoco 模体肽的 C 端部分,使其在与 Gα(i1)结合时采用新的构象。重新设计的复合物的 X 射线晶体结构与计算模型非常匹配,骨架均方根偏差为 1.1 Å。