Rao Francesco, Caflisch Amedeo
Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057, Switzerland.
J Mol Biol. 2004 Sep 3;342(1):299-306. doi: 10.1016/j.jmb.2004.06.063.
The conformation space of a 20 residue antiparallel beta-sheet peptide, sampled by molecular dynamics simulations, is mapped to a network. Snapshots saved along the trajectory are grouped according to secondary structure into nodes of the network and the transitions between them are links. The conformation space network describes the significant free energy minima and their dynamic connectivity without requiring arbitrarily chosen reaction coordinates. As previously found for the Internet and the World-Wide Web as well as for social and biological networks, the conformation space network is scale-free and contains highly connected hubs like the native state which is the most populated free energy basin. Furthermore, the native basin exhibits a hierarchical organization, which is not found for a random heteropolymer lacking a predominant free-energy minimum. The network topology is used to identify conformations in the folding transition state (TS) ensemble, and provides a basis for understanding the heterogeneity of the TS and denatured state ensemble as well as the existence of multiple pathways.
通过分子动力学模拟采样得到的一条20个残基的反平行β折叠肽的构象空间被映射到一个网络上。沿着轨迹保存的快照根据二级结构被分组到网络的节点中，它们之间的转变则为链接。构象空间网络描述了显著的自由能最小值及其动态连通性，而无需任意选择反应坐标。正如之前在互联网、万维网以及社会和生物网络中所发现的那样，构象空间网络是无标度的，并且包含像天然状态这样高度连接的枢纽，天然状态是占据最多的自由能盆地。此外，天然盆地呈现出一种层次结构，这在缺乏主要自由能最小值的随机杂聚物中是找不到的。网络拓扑结构被用于识别折叠过渡态（TS）系综中的构象，并为理解TS和变性态系综的异质性以及多条途径的存在提供了基础。
