DeLano W L, Brünger A T
Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520.
Proteins. 1994 Oct;20(2):105-23. doi: 10.1002/prot.340200202.
A simulated annealing method for atomic resolution structure prediction of alpha-helical coiled coil proteins is described which draws upon knowledge of the oligomerization state, the helix directionality, and the properties of heptad repeat sequences. Unknown structural parameters, such as the coiled coil twist angle and the side chain conformations, are heavily sampled while allowing for flexibility in the helix backbone geometry. Structures of the wild-type GCN4 dimer [O'Shea et al., Science 254:539-544, 1991] and a mutant tetramer [Harbury et al., Science 292:1401-1407, 1993] have been generated and compared with the X-ray crystal structures. The wild-type dimer model has a root mean square coordinate deviation from the crystal structure of 0.73 A for nonhydrogen atoms in the dimerization interface. Structures of a mutant dimer and a mutant trimer have been predicted. Packing energetics were analyzed for core leucine and isoleucine side chains in dimeric and tetrameric coiled coils. Strong packing preferences were found in the dimers but not in the tetramers. Thus, packing in the dimer may be responsible for the switch from a two-stranded to a four-stranded coiled coil caused by the GCN4 leucine zipper mutations.
本文描述了一种用于预测α-螺旋卷曲螺旋蛋白原子分辨率结构的模拟退火方法，该方法借鉴了寡聚化状态、螺旋方向性以及七肽重复序列特性等方面的知识。在允许螺旋主链几何结构具有灵活性的同时，对未知结构参数（如卷曲螺旋扭转角和侧链构象）进行了大量采样。已生成野生型GCN4二聚体[奥谢等人，《科学》254:539 - 544，1991]和突变体四聚体[哈伯里等人，《科学》292:1401 - 1407，1993]的结构，并与X射线晶体结构进行了比较。野生型二聚体模型在二聚化界面中，非氢原子与晶体结构的均方根坐标偏差为0.73埃。已预测了突变体二聚体和突变体三聚体的结构。对二聚体和四聚体卷曲螺旋中核心亮氨酸和异亮氨酸侧链的堆积能量进行了分析。在二聚体中发现了强烈的堆积偏好，而在四聚体中则没有。因此，二聚体中的堆积可能是由GCN4亮氨酸拉链突变导致的从双链卷曲螺旋向四链卷曲螺旋转变的原因。
