Head-Gordon T, Stillinger F H, Wright M H, Gay D M
AT&T Bell Laboratories, Murray Hill, NJ 07974.
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11513-7. doi: 10.1073/pnas.89.23.11513.
We present a proposition, the "poly(L-alanine) hypothesis," which asserts that the native backbone geometry for any polypeptide or protein of M residues has a closely mimicking, mechanically stable, image in poly(L-alanine) of the same number of residues. Using a molecular mechanics force field to represent the relevant potential energy hypersurfaces, we have carried out calculations over a wide range of M values to show that poly(L-alanine) possesses the structural versatility necessary to satisfy the proposition. These include poly(L-alanine) representatives of minima corresponding to secondary and supersecondary structures, as well as poly(L-alanine) images for tertiary structures of the naturally occurring proteins bovine pancreatic trypsin inhibitor, crambin, ribonuclease A, and superoxide dismutase. The successful validation of the hypothesis presented in this paper indicates that poly(L-alanine) will serve as a good reference material in thermodynamic perturbation theory and calculations aimed at evaluating relative free energies for competing candidate tertiary structures in real polypeptides and proteins.
我们提出了一个命题，即“聚（L-丙氨酸）假说”，该假说认为，对于任何含有M个残基的多肽或蛋白质，其天然主链几何结构在相同数量残基的聚（L-丙氨酸）中具有紧密模拟且机械稳定的镜像。我们使用分子力学力场来表示相关的势能超曲面，针对广泛的M值进行了计算，以表明聚（L-丙氨酸）具备满足该命题所需的结构多样性。这些包括对应于二级和超二级结构的聚（L-丙氨酸）极小值代表，以及天然存在的蛋白质牛胰蛋白酶抑制剂、克拉宾、核糖核酸酶A和超氧化物歧化酶三级结构的聚（L-丙氨酸）镜像。本文所提出假说的成功验证表明，聚（L-丙氨酸）将作为热力学微扰理论以及旨在评估真实多肽和蛋白质中竞争候选三级结构相对自由能的计算中的良好参考材料。
