DeWitte R S, Michnick S W, Shakhnovich E I
Department of Chemistry, Harvard University, Cambridge Massachusetts 02138, USA.
Protein Sci. 1995 Sep;4(9):1780-91. doi: 10.1002/pro.5560040913.
We present an efficient new algorithm that enumerates all possible conformations of a protein that satisfy a given set of distance restraints. Rapid growth of all possible self-avoiding conformations on the diamond lattice provides construction of alpha-carbon representations of a protein fold. We investigated the dependence of the number of conformations on pairwise distance restraints for the proteins crambin, pancreatic trypsin inhibitor, and ubiquitin. Knowledge of between one and two contacts per monomer is shown to be sufficient to restrict the number of candidate structures to approximately 1,000 conformations. Pairwise RMS deviations of atomic position comparisons between pairs of these 1,000 structures revealed that these conformations can be grouped into about 25 families of structures. These results suggest a new approach to assessing alternative protein folds given a very limited number of distance restraints. Such restraints are available from several experimental techniques such as NMR, NOESY, energy transfer fluorescence spectroscopy, and crosslinking experiments. This work focuses on exhaustive enumeration of protein structures with emphasis on the possible use of NOESY-determined distance restraints.
我们提出了一种高效的新算法，该算法可枚举满足给定距离约束集的蛋白质的所有可能构象。菱形晶格上所有可能的自回避构象的快速增长为蛋白质折叠的α-碳表示提供了构建方法。我们研究了对于克拉宾蛋白、胰腺胰蛋白酶抑制剂和泛素，构象数量对成对距离约束的依赖性。结果表明，每个单体知道一到两个接触足以将候选结构的数量限制到大约1000种构象。这1000种结构之间的原子位置比较的成对均方根偏差表明，这些构象可以分为大约25个结构家族。这些结果表明，在距离约束数量非常有限的情况下，有一种评估蛋白质替代折叠的新方法。这种约束可从多种实验技术获得，如核磁共振（NMR）、核欧沃豪斯效应光谱（NOESY）、能量转移荧光光谱和交联实验。这项工作重点在于对蛋白质结构进行穷举枚举，尤其强调可能使用由NOESY确定的距离约束。
