Chan H S, Dill K A
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143-1204, USA.
Proteins. 1996 Mar;24(3):335-44. doi: 10.1002/(SICI)1097-0134(199603)24:3<335::AID-PROT6>3.0.CO;2-F.
Proteins fold to unique compact native structures. Perhaps other polymers could be designed to fold in similar ways. The chemical nature of the monomer "alphabet" determines the "energy matrix" of monomer interactions-which defines the folding code, the relationship between sequence and structure. We study two properties of energy matrices using two-dimensional lattice models: uniqueness, the number of sequences that fold to only one structure, and encodability, the number of folds that are unique lowest-energy structures of certain monomer sequences. For the simplest model folding code, involving binary sequences of H (hydrophobic) and P (polar) monomers, only a small fraction of sequences fold uniquely, and not all structures can be encoded. Adding strong repulsive interactions results in a folding code with more sequences folding uniquely and more designable folds. Some theories suggest that the quality of a folding code depends only on the number of letters in the monomer alphabet, but we find that the energy matrix itself can be at least as important as the size of the alphabet. Certain multi-letter codes, including some with 20 letters, may be less physical or protein-like than codes with smaller numbers of letters because they neglect correlations among inter-residue interactions, treat only maximally compact conformations, or add arbitrary energies to the energy matrix.
蛋白质折叠成独特的紧密天然结构。或许可以设计其他聚合物以类似方式折叠。单体“字母表”的化学性质决定了单体相互作用的“能量矩阵”，而这又定义了折叠密码，即序列与结构之间的关系。我们使用二维晶格模型研究能量矩阵的两个性质：唯一性，即折叠成单一结构的序列数量；可编码性，即某些单体序列的唯一最低能量结构的折叠数量。对于最简单的折叠密码模型，涉及H（疏水）和P（极性）单体的二元序列，只有一小部分序列能唯一折叠，且并非所有结构都能被编码。添加强排斥相互作用会产生一种折叠密码，有更多序列能唯一折叠，且有更多可设计的折叠。一些理论认为折叠密码的质量仅取决于单体字母表中的字母数量，但我们发现能量矩阵本身至少与字母表大小同样重要。某些多字母密码，包括一些有20个字母的密码，可能不如字母数量较少的密码那样符合实际或类似蛋白质，因为它们忽略了残基间相互作用的相关性，只考虑了最大程度紧密的构象，或者给能量矩阵添加了任意能量。
