Interplay among tertiary contacts, secondary structure formation and side-chain packing in the protein folding mechanism:: All-atom representation study of protein L
Interplay among tertiary contacts, secondary structure formation and side-chain packing in the protein folding mechanism:: All-atom representation study of protein L
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DOI：
10.1016/s0022-2836(02)01379-7
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发表时间：
2003-02-21
影响因子：
5.6
通讯作者：
Onuchic, JN
中科院分区：
文献类型：
--
作者：
Clementi, C;García, AE;Onuchic, JN
实验和理论结果表明，由于蛋白质是积极最低限度的挫折，本机折叠，或拓扑结构，起着主要作用，在确定的过渡态系综的结构和对途径的中间状态在蛋白质折叠。虽然中心作用的天然状态拓扑结构在确定折叠机制被认为是一个相当普遍的结果，至少对于小的双态折叠蛋白质，有显着的例外。最近的实验结果表明，仅靠拓扑结构并不总能决定折叠机制，并证明拓扑结构和能量之间的平衡非常微妙。这种平衡似乎在具有高度对称的天然结构的蛋白质中特别关键，例如蛋白质L和G，它们具有通过不同机制向外折叠的相似天然结构拓扑。简化的仅C-α原子的蛋白质模型已显示不足以区分这些机制。全原子围棋模型提供了一个有价值的中间模型之间的结构简化的蛋白质表示和全原子蛋白质模拟与显式/隐式溶剂描述。我们在这里提出了一个详细的研究的全原子G（o）在酒吧样表示的蛋白质L，在密切比较的实验结果和从一个简单的C-α原子表示相同的蛋白质的结果。我们还对蛋白质G进行了模拟，在那里我们获得了一种折叠机制，其中蛋白质对称性以与实验观察到的蛋白质L相反的方式被破坏。蛋白L的详细分析还表明，特定残基的作用是正确和定量再现的全原子G（o）在酒吧模型几乎整个蛋白质。(C)2003爱思唯尔科技有限公司版权所有。
Experimental and theoretical results suggest that, since proteins are energetically minimally frustrated, the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble and on-pathway intermediate states in protein folding. Although the central role of native state topology in determining the folding mechanism is thought to be a quite general result-at least for small two-state folding proteins-there are remarkable exceptions. Recent experimental findings have shown that topology alone cannot always determine the folding mechanism, and demonstrated that the balance between topology and energetics is very delicate. This balance seems to be particularly critical in proteins with a highly symmetrical native structure, such as proteins L and G, which have similar native structure topology Out fold by different mechanisms. Simplified, C-alpha-atom only protein models have shown not be sufficient to differentiate these mechanisms. An all-atom Go model provides a valuable intermediate model between structurally simplified protein representations and all-atom protein simulations with explicit/implicit solvent descriptions. We present here a detailed study of an all-atom G (o) over bar -like representation of protein L, in close comparison with the experimental results and with the results obtained from a simple C-alpha-atom representation of the same protein. We also perform simulations for protein G, where we obtain a folding mechanism in which the protein symmetry is broken exactly in the opposite way to protein L as has been observed experimentally. A detailed analysis for protein L also shows that the role of specific residues is correctly and quantitatively reproduced by the all-atom G (o) over bar model over almost the entire protein. (C) 2003 Elsevier Science Ltd. All rights reserved.