Tanaka S, Scheraga H A
Proc Natl Acad Sci U S A. 1975 Oct;72(10):3802-6. doi: 10.1073/pnas.72.10.3802.
A hypothesis for protein folding is proposed, in which the native structure is formed by a three-step mechanism: (A) formation of ordered backbone structures by short-range interactions, (B) formation of small contact regions by medium-range interactions, and (C) association of the small contact regions into the native structure by long-range interactions. Empirical interaction parameters (free energy of formation of a contact) between amino-acid residues were evaluated from the frequency of contacts in the x-ray structures of native proteins. On the basis of this mechanism, a Monte Carlo simulation of protein folding (with an accompanying decrease in the total contact free energy) was carried out for bovine pancreatic trypsin inhibitor. The predicted three-dimensional structure is in fairly good agreement with the experimental one.
提出了一种蛋白质折叠假说，其中天然结构通过三步机制形成：(A) 通过短程相互作用形成有序的主链结构，(B) 通过中程相互作用形成小的接触区域，以及 (C) 通过长程相互作用将小的接触区域缔合形成天然结构。根据天然蛋白质X射线结构中的接触频率评估了氨基酸残基之间的经验相互作用参数（形成一个接触的自由能）。基于此机制，对牛胰蛋白酶抑制剂进行了蛋白质折叠的蒙特卡罗模拟（伴随着总接触自由能的降低）。预测的三维结构与实验结构相当吻合。
