Energy Matrix of Structurally Important Side-Chain/Side-Chain Interactions in Proteins
Energy Matrix of Structurally Important Side-Chain/Side-Chain Interactions in Proteins
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DOI：
10.1021/ct100007y
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发表时间：
2010-07-01
影响因子：
5.5
通讯作者：
Vondrasek, Jiri
中科院分区：
文献类型：
--
作者：
Berka, Karel;Laskowski, Roman A.;Vondrasek, Jiri
蛋白质中氨基酸侧链之间的相互作用通常被认为是控制多肽链精确排列成明确空间结构的最重要的稳定因素。我们使用RI-DFT-D方法计算了所有氨基酸侧链之间的全部20×20相互作用能矩阵。对于每一对，我们使用从蛋白质数据库(PDB)中对已知蛋白质结构的分析中提取的具有代表性的3D构象。该代表来自两个侧链的相对取向的最大簇。我们发现，除了具有相同总电荷的侧链对外，所有计算的氨基酸对之间的相互作用能在气相中都是有吸引力的。我们将这些数据与PARM03和OPLSAA/L力场计算的结果进行了比较，以考察简单方法模拟生物分子及其行为的可靠性。力场为我们的集合产生了良好的整体相互作用能量，但在评估某些特定的相互作用时存在问题，这些相互作用对蛋白质稳定性可能是主要重要的。然后，我们详细研究了涉及色氨酸的20个侧链相互作用。相互作用能量的直方图表明，相互作用能量的分布既不是正态的，也不是玻耳兹曼式的，而且我们的代表几何主要对应于最小能量几何，而最小能量几何在整个成对能量分布中填充得很少。我们认为，基于几何准则的簇化算法得到的团簇代表不能被认为是整个侧链/侧链相互作用分布的典型相互作用。它们似乎集中体现了蛋白质中最强的相互作用，通常在功能或结构上都很重要。
The interactions between amino acid side chains in proteins are generally considered to be the most important stabilizing factor controlling the precise arrangement of the polypeptide chain into a well-defined spatial structure. We used the RI-DFT-D method to calculate the full 20 x 20 matrix of interaction energies between all pairs of amino acid side chains. For each pair, we used a representative 3D conformation extracted from an analysis of known protein structures from Protein Data Bank (PDB). The representative comes from the largest cluster of relative orientations of the two side chains. We find that all of the calculated interaction energies between selected pairs of amino acids are attractive in the gas phase with the exception of side chain pairs having the same total charge. We compared these data with those calculated by the parm03 and OPLS-AA/L force fields to investigate the reliability of simple methods in modeling biomolecules and their behavior. The force fields yield good overall interaction energies for our set but have problems in evaluation of some particular interactions which could be of principal importance for protein stability. We then looked in detail at the 20 side chain interactions involving tryptophan. The histograms of interaction energies showed that the distributions of the interaction energies are neither normal nor Boltzmann-like and that our representative geometries correspond mostly to the minimum energy geometry which is rather poorly populated in the whole pairwise energy distribution. We concluded that cluster representatives obtained by the clusterization algorithm based on geometry criteria cannot be considered as a typical interaction for the whole side chain/side chain interaction distribution. They seem to epitomize the strongest interactions in a protein and are often functionally or structurally important.