Dill K A, Bromberg S, Yue K, Fiebig K M, Yee D P, Thomas P D, Chan H S
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143-1204, USA.
Protein Sci. 1995 Apr;4(4):561-602. doi: 10.1002/pro.5560040401.
General principles of protein structure, stability, and folding kinetics have recently been explored in computer simulations of simple exact lattice models. These models represent protein chains at a rudimentary level, but they involve few parameters, approximations, or implicit biases, and they allow complete explorations of conformational and sequence spaces. Such simulations have resulted in testable predictions that are sometimes unanticipated: The folding code is mainly binary and delocalized throughout the amino acid sequence. The secondary and tertiary structures of a protein are specified mainly by the sequence of polar and nonpolar monomers. More specific interactions may refine the structure, rather than dominate the folding code. Simple exact models can account for the properties that characterize protein folding: two-state cooperativity, secondary and tertiary structures, and multistage folding kinetics--fast hydrophobic collapse followed by slower annealing. These studies suggest the possibility of creating "foldable" chain molecules other than proteins. The encoding of a unique compact chain conformation may not require amino acids; it may require only the ability to synthesize specific monomer sequences in which at least one monomer type is solvent-averse.
蛋白质结构、稳定性和折叠动力学的一般原理最近在简单精确晶格模型的计算机模拟中得到了探索。这些模型在基本层面上表示蛋白质链，但它们涉及的参数、近似值或隐含偏差很少，并且允许对构象和序列空间进行完整的探索。此类模拟得出了一些可检验的预测，这些预测有时是意想不到的：折叠密码主要是二元的，并且在整个氨基酸序列中是离域的。蛋白质的二级和三级结构主要由极性和非极性单体的序列决定。更具体的相互作用可能会优化结构，而不是主导折叠密码。简单精确模型可以解释蛋白质折叠的特征性质：两态协同性、二级和三级结构以及多阶段折叠动力学——快速的疏水塌缩随后是较慢的退火过程。这些研究表明，有可能创造出除蛋白质之外的“可折叠”链状分子。编码独特的紧密链构象可能不需要氨基酸；可能只需要能够合成特定的单体序列，其中至少有一种单体类型是疏溶剂的。
