The Dynameomics project contains native state and unfolding simulations of 807 protein domains, where each domain is representative of a different metafold; these metafolds encompass ~97% of protein fold space. There is a long-standing question in structural biology as to whether proteins in the same fold family share the same folding/unfolding characteristics. Using molecular dynamics simulations from the Dynameomics project, we conducted a detailed study of protein unfolding/folding pathways for 5 protein domains from the immunoglobulin (Ig)-like β-sandwich metafold (the highest ranked metafold in our database). The domains have sequence similarities ranging from 4 to 15% and are all from different SCOP superfamilies, yet they share the same overall Ig-like topology. Despite having very different amino acid sequences, the dominant unfolding pathway is very similar for the 5 proteins, and the secondary structures that are peripheral to the aligned, shared core domain add variability to the unfolding pathway. Aligned residues in the core domain display consensus structure in the transition state primarily through conservation of hydrophobic positions. Commonalities in the obligate folding nucleus indicate that insights into the major events in the folding/unfolding of other domains from this metafold may be obtainable from unfolding simulations of a few representative proteins.

中文翻译：

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不相关的免疫球蛋白样β夹心蛋白的共同展开途径。

Dynameomics项目包含807个蛋白质结构域的原始状态和展开模拟，其中每个结构域代表一个不同的元折叠。这些元折叠包含约97％的蛋白质折叠空间。结构生物学中存在一个长期存在的问题，即同一折叠家族中的蛋白质是否共享相同的折叠/展开特征。使用来自Dynameomics项目的分子动力学模拟，我们对免疫球蛋白（Ig）样β-三明治元折叠（在我们数据库中排名最高的元折叠）的5个蛋白质域的蛋白质展开/折叠途径进行了详细研究。这些域的序列相似性范围为4％至15％，均来自不同的SCOP超家族，但它们共有相同的整体Ig样拓扑。尽管氨基酸序列非常不同，对于5种蛋白质，主要的解折叠途径非常相似，位于对齐的共享核心结构域外围的二级结构为解折叠途径增加了可变性。核心结构域中的比对残基主要通过疏水位置的保守而在过渡状态下显示共有结构。专性折叠核的共同性表明，可以从一些代表性蛋白质的展开模拟中获得有关此域折叠中其他域折叠/展开中主要事件的见解。核心结构域中的比对残基主要通过疏水位置的保守而在过渡状态下显示共有结构。专性折叠核的共同性表明，可以从一些代表性蛋白质的展开模拟中获得有关此域折叠中其他域折叠/展开中主要事件的见解。核心结构域中的比对残基主要通过疏水位置的保守而在过渡状态下显示共有结构。专性折叠核的共同性表明，可以从一些代表性蛋白质的展开模拟中获得有关此域折叠中其他域折叠/展开中主要事件的见解。