Lesk A M, Rose G D
Proc Natl Acad Sci U S A. 1981 Jul;78(7):4304-8. doi: 10.1073/pnas.78.7.4304.
We present a method to identify all compact, contiguous-chain, structural units in a globular protein from x-ray coordinates. These units are then used to describe a complete set of hierarchic folding pathways for the molecule. Our analysis shows that the larger units are combinations of smaller units, giving rise to a structural hierarchy ranging from the whole protein monomer through supersecondary structures down to individual helices and strands. It turns out that there is more than one way to assemble the protein by self-association of its compact units. However, the number of possible pathways is small--small enough to be exhaustively explored by a computer program. The hierarchic organization of compact units in protein molecules is consistent with a model for folding by hierarchic condensation. In this model, neighboring hydrophobic chain sites interact to form folding clusters, with further stepwise cluster association giving rise to a population of folding intermediates.
我们提出了一种从X射线坐标中识别球状蛋白质中所有紧密、连续链结构单元的方法。然后，这些单元被用于描述该分子完整的一套层次折叠途径。我们的分析表明，较大的单元是较小单元的组合，从而产生了一个结构层次，从整个蛋白质单体到超二级结构，再到单个螺旋和链。结果发现，通过其紧密单元的自组装来组装蛋白质的方式不止一种。然而，可能的途径数量很少——少到足以被计算机程序彻底探索。蛋白质分子中紧密单元的层次组织与层次凝聚折叠模型是一致的。在这个模型中，相邻的疏水链位点相互作用形成折叠簇，进一步的逐步簇关联产生了一群折叠中间体。
