The structural distribution of cooperative interactions in proteins: Analysis of the native state ensemble
The structural distribution of cooperative interactions in proteins: Analysis of the native state ensemble
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DOI：
10.1073/pnas.95.17.9903
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发表时间：
1998-08-18
影响因子：
11.1
通讯作者：
Freire, E
中科院分区：
文献类型：
--
作者：
Hilser, VJ;Dowdy, D;Freire, E
协同相互作用将蛋白质分子内不同氨基酸残基的行为联系起来。因此，化学或物理扰动对任何给定残基的影响会通过复杂的相互作用网络传播到其他残基。很多时候，氨基酸“感知”蛋白质分子中非常遥远的位置发生的扰动的影响。在这些研究中，我们通过计算机模拟研究了这些相互作用的结构分布。我们在此表明，协作相互作用本质上不是双向的，并且不同的残基在蛋白质中存在的复杂相互作用网络中发挥着不同的作用。对残基 j 的扰动对残基 k 的影响不一定等于对残基 k 的相同扰动对残基 j 的影响。在本文中，我们介绍了一种旨在绘制蛋白质内协作相互作用网络的计算机算法。该算法详尽地对蛋白质中的每个残基进行单位点热力学突变，并检查这些突变对构象状态分布的影响。该算法已应用于三种不同的蛋白质（lambda 阻遏片段 6-85、胰凝乳蛋白酶抑制剂 2 和 barnase），该算法很好地解释了观察到的这些蛋白质的行为。
Cooperative interactions link the behavior of different amino acid residues within a protein molecule, As a result, the effects of chemical or physical perturbations to any given residue are propagated to other residues by an intricate network of interactions. Very often, amino acids "sense" the effects of perturbations occurring at very distant locations in the protein molecule. In these studies, we have investigated by computer simulation the structural distribution of those interactions, We show here that cooperative interactions are not intrinsically bi-directional and that different residues play different roles within the intricate network of interactions existing in a protein. The effect of a perturbation to residue j on residue k is not necessarily equal to the effect of the same perturbation to residue k on residue j, In this paper, we introduce a computer algorithm aimed at mapping the network of cooperative interactions within a protein. This algorithm exhaustively performs single site thermodynamic mutations to each residue in the protein and examines the effects of those mutations on the distribution of conformational states. The algorithm has been applied to three different proteins (lambda repressor fragment 6-85, chymotrypsin inhibitor 2, and barnase), This algorithm accounts well for the observed behavior of these proteins.