Cooperativity in amide hydrogen bonding chains: Implications for protein-folding models
Cooperativity in amide hydrogen bonding chains: Implications for protein-folding models
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DOI：
10.1021/ja004271l
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发表时间：
2001-05-09
影响因子：
15
通讯作者：
Dannenberg, JJ
中科院分区：
文献类型：
--
作者：
Kobko, N;Paraskevas, L;Dannenberg, JJ
蛋白质折叠是一个重要但仍相对知之甚少的领域，对许多重要的生化过程具有许多影响。有几篇评论1, 2 与蛋白质折叠的化学过程相关。最近整期的《化学研究报告》专门讨论了这个主题。 3 折叠过程的动力学通常使用蒙特卡罗技术在使用各个最近邻接触定义的潜在表面上进行研究。虽然成对接触势的使用被批评为不充分，但也有报道称，使用有效的二体势来模拟多体问题4取得了成功。 5 在本次通讯中，我们提供的数据揭示了甲酰胺分子氢键链异常高的协同性。蛋白质中也形成类似的链。就此处讨论的氢键链与蛋白质中的氢键链相似而言，用于模拟多肽中类似氢键的成对势可能会导致误导性结果。最近在 DFT 和分子力学研究中报道了 N-甲基甲酰胺与甲酸盐的配合物内的协同作用。 6 越来越明显的是，涉及许多分子的协同相互作用是分子间相互作用的重要组成部分，特别是涉及氢键的相互作用。这些合作相互作用在固态中尤其重要。在气相中，分子太过分离而无法协同相互作用。在液相中，最近邻分子的动态变化限制了协同性的重要性。许多分子晶体涉及氢键相互作用。一个具体的例子是1, 3-环己二酮的烯醇。该分子的晶体结构包含无限的氢键链。氢键上的 O...O 距离非常短 (2.58 Å)，7 意味着强相互作用，可能是共价相互作用。 CC 和 CdC 键在晶体中分别缩短和延长，CO 和 CdO 键也是如此。这种类型的相互作用被称为共振辅助氢键（RAHB）。 8 正如人们所预料的那样，分子轨道计算表明强大的协同成分在分子间相互作用中发挥着重要作用。这些氢键很少被描述为静电相互作用。 9 他们非常合作。 10使用 GAUSSIAN 98 计算机程序套件对 2 至 10 个甲酰胺分子的氢键链进行 HF/D95** 和 B3LYP/D95** 水平的 Hartree-Fock (HF) 和密度泛函理论 (DFT) 计算。 11 B3LYP 方法将 Becke 的 3 参数泛函 12 与 Lee、Yang 和 Parr 的相关泛函提供的非局部相关性相结合。 13 氢键链经过完全优化，限制每个甲酰胺分子在几何上等价且与其他分子共面。分子间几何参数完全不受限制。分子排列如图 1 所示。计算振动频率以获得二聚体的焓和基组叠加误差 (BSSE) 的平衡 (CP) 校正。这些值被用作较大链的校正，假设振动和 CP 校正都被视为累加。以这种方式，二聚体（一个氢键）的九倍振动和CP校正被用于十聚体（九个氢键）。该假设的有效性在包含两到五种甲酰胺的完全优化的小聚集体上进行了测试。这 …
Protein folding is an important, yet still relatively poorly understood, field with many implications for a number of important biochemical processes. There have been several reviews1, 2 that are relevant to the chemical processes of protein folding. An entire issue of Accounts of Chemical Research was recently dedicated to this topic. 3 The dynamics of the folding process is typically studied using Monte Carlo techniques on a potential surface defined using the individual nearest neighbor contacts. While use of pairwise contact potentials has been criticized as inadequate, 4 success in using effective two-body potentials to simulate a manybody problem has also been reported. 5 In this communication we present data that reveals an unusually high degree of cooperativity for hydrogen-bonding chains of formamide molecules. Similar chains form in proteins. To the extent that the H-bonding chains discussed here resemble those in proteins, the pairwise potentials that have been used to model the analogous hydrogen bonds in polypeptides might lead to misleading results. Cooperativity within complexes of N-methylformamides with formate has been recently reported in a DFT and molecular mechanics study. 6 It is becoming increasingly apparent that cooperative interactions involving many molecules is an important component of intermolecular interactions, particularly those involving hydrogen bonds. These cooperative interactions are particularly important in the solid-state. In the gas phase, molecules are too separated to interact cooperatively. In the liquid phase, dynamic changes in the nearest neighbor molecules limit the importance of cooperativity. Many molecular crystals involve hydrogen-bonding interactions. A particular example is that of the enol of 1, 3-cyclohexanedione. The crystal structure of this molecule involves infinite hydrogen bonding chains. The O... O distance across the hydrogen bond is quite short (2.58 Å), 7 implying a strong, possibly covalent, interaction. The CC and CdC bonds shorten and lengthen respectively in the crystal, as do the CO and CdO bonds. Interactions of this type have been referred to as resonance assisted hydrogen bonds (RAHB). 8 As one might expect, molecular orbital calculations indicate a strong cooperative component plays an important role in the intermolecular interactions. These H-bonds are poorly described as electrostatic interactions. 9 They are highly cooperative. 10Hartree-Fock (HF) and density functional theory (DFT) calculations at the HF/D95** and B3LYP/D95** levels were performed on H-bonding chains of from two to ten formamide molecules using the GAUSSIAN 98 suite of computer programs. 11 The B3LYP method combines Becke’s 3-parameter functional, 12 with the nonlocal correlation provided by the correlation functional of Lee, Yang and Parr. 13 The H-bonding chains were completely optimized with the restraint that each formamide molecule be geometrically equivalent and coplanar with the others. The intermolecular geometrical parameters were completely unrestrained. Molecules were arranged as in Figure 1. Vibrational frequencies were calculated to obtain the enthalpy and counterpoise (CP) corrections for basis set superposition error (BSSE) were calculated for the dimers. These values were used as corrections for the larger chains using the assumption that both the vibrational and CP corrections would be treated as additive. In this manner, nine times the vibrational and CP corrections for the dimer (one H-bond) are used for the decamer (nine H-bonds). The validity of this assumption was tested on fully optimized small aggregates containing from two to five formamides. The …