Karpen M E, de Haseth P L, Neet K E
Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106.
Proteins. 1989;6(2):155-67. doi: 10.1002/prot.340060206.
An efficient algorithm was characterized that determines the similarity in main chain conformation between short protein substructures. The algorithm computes delta t, the root mean square difference in phi and psi torsion angles over a small number of amino acids (typically 3-5). Using this algorithm, large numbers of protein substructure comparisons were feasible. The parameter delta t was sensitive to variations in local protein conformation, and it correlates with delta r, the root mean square deviation in atomic coordinates. Values for delta t were obtained that define similarity thresholds, which determine whether two substructures are considered structurally similar. To set a lower bound on the similarity threshold, we estimated the component of delta t due to measurement noise from comparisons of independently refined coordinates of the same protein. A sample distribution of delta t from nonhomologous protein comparisons identified an upper bound on the similarity threshold, one that refrains from incorporating large numbers of nonmatching comparisons. Unlike methods based on C alpha atoms alone, delta t was sensitive to rotations in the peptide plane, shown to occur in several proteins. Comparisons of homologous proteins by delta t showed that the active site torsion angles are highly conserved. The delta t method was applied to the alpha-chain of human hemoglobin, where it readily demonstrated the local differences in the structures of different ligation states.
一种高效算法得以确定，该算法可判定短蛋白质亚结构之间主链构象的相似性。该算法计算δt，即少量氨基酸（通常为3 - 5个）上φ和ψ扭转角的均方根差。利用此算法，大量蛋白质亚结构比较变得可行。参数δt对局部蛋白质构象的变化敏感，且它与原子坐标的均方根偏差δr相关。获得了定义相似性阈值的δt值，这些阈值决定了两个亚结构是否被视为结构相似。为设定相似性阈值的下限，我们通过比较同一蛋白质独立精制坐标的测量噪声来估计δt的组成部分。来自非同源蛋白质比较的δt样本分布确定了相似性阈值的上限，该上限避免纳入大量不匹配的比较。与仅基于Cα原子的方法不同，δt对肽平面中的旋转敏感，这在几种蛋白质中已得到证实。通过δt对同源蛋白质进行比较表明，活性位点扭转角高度保守。δt方法应用于人类血红蛋白的α链，它很容易展示出不同连接状态结构中的局部差异。
