Saven J G, Wolynes P G
School of Chemical Sciences, University of Illinois, Urbana, 61801, USA.
J Mol Biol. 1996 Mar 22;257(1):199-216. doi: 10.1006/jmbi.1996.0156.
We investigate the role that local conformational tendencies can have in guiding the folding of helical proteins, using simple statistical mechanical models. The theory provides a synthesis of classical models of the helix-coil transition in polymers with an approximate treatment of the effects of excluded volume, confinement, and packing alignment of the helices based on a free energy function. The theory studies the consequences of signals encoded locally in the sequence as stabilization energies associated with three types of local structure: native helical conformations, native non-helical conformations, and native helix caps or start-stop signals. The role of randomness in the energies of conformations due to tertiary interactions is also studied vis-à-vis the difficulty of conformational search. The thermal behavior of the model is presented for realistic values of the conformational signal energies, which can be estimated from experimental studies on peptide fragments. Estimates are made for the relative contribution of local signals and specific tertiary interactions to the folding stability gap.
我们使用简单的统计力学模型，研究局部构象倾向在指导螺旋蛋白折叠中所起的作用。该理论将聚合物中螺旋 - 线圈转变的经典模型与基于自由能函数对排除体积、限制和螺旋堆积排列效应的近似处理相结合。该理论研究了序列中局部编码信号作为与三种局部结构相关的稳定能的后果：天然螺旋构象、天然非螺旋构象以及天然螺旋帽或起始 - 终止信号。还针对构象搜索的难度研究了三级相互作用导致的构象能量随机性的作用。针对构象信号能量的实际值给出了模型的热行为，这些值可从肽片段的实验研究中估算得出。对局部信号和特定三级相互作用对折叠稳定性差距的相对贡献进行了估算。
