State Key Laboratory of Non-food Biomass Energy and Enzyme Technology, National Engineering Research Center for Non-food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, Guangxi 530007, People's Republic of China.
J Comput Chem. 2012 Jan 15;33(2):153-62. doi: 10.1002/jcc.21951. Epub 2011 Oct 14.
Cation-π interaction is comparable and as important as other main molecular interaction types, such as hydrogen bond, electrostatic interaction, van der Waals interaction, and hydrophobic interaction. Cation-π interactions frequently occur in protein structures, because six (Phe, Tyr, Trp, Arg, Lys, and His) of 20 natural amino acids and all metallic cations could be involved in cation-π interaction. Cation-π interactions arise from complex physicochemical nature and possess unique interaction behaviors, which cannot be modeled and evaluated by existing empirical equations and force field parameters that are widely used in the molecular dynamics. In this study, the authors present an empirical approach for cation-π interaction energy calculations in protein interactions. The accurate cation-π interaction energies of aromatic amino acids (Phe, Tyr, and Try) with protonated amino acids (Arg and Lys) and metallic cations (Li(+), Na(+), K(+), and Ca(2+)) are calculated using B3LYP/6-311+G(d,p) method as the benchmark for the empirical formulization and parameterization. Then, the empirical equations are built and the parameters are optimized based on the benchmark calculations. The cation-π interactions are distance and orientation dependent. Correspondingly, the empirical equations of cation-π interactions are functions of two variables, the distance r and the orientation angle θ. Two types of empirical equations of cation-π interactions are proposed. One is a modified distance and orientation dependent Lennard-Jones equation. The second is a polynomial function of two variables r and θ. The amino acid-based empirical equations and parameters provide simple and useful tools for evaluations of cation-π interaction energies in protein interactions.
阳离子-π 相互作用可与氢键、静电相互作用、范德华相互作用和疏水相互作用等其他主要分子相互作用类型相媲美，同样重要。阳离子-π 相互作用经常出现在蛋白质结构中，因为 20 种天然氨基酸中的 6 种（苯丙氨酸、色氨酸、色氨酸、精氨酸、赖氨酸和组氨酸）和所有金属阳离子都可能参与阳离子-π 相互作用。阳离子-π 相互作用源于复杂的物理化学性质，并具有独特的相互作用行为，这不能通过现有的经验方程和力场参数来建模和评估，这些经验方程和力场参数广泛应用于分子动力学中。在这项研究中，作者提出了一种用于计算蛋白质相互作用中阳离子-π 相互作用能的经验方法。使用 B3LYP/6-311+G(d,p)方法作为基准，计算芳香族氨基酸（苯丙氨酸、色氨酸和色氨酸）与质子化氨基酸（精氨酸和赖氨酸）和金属阳离子（Li(+)、Na(+)、K(+)和 Ca(2+)）之间准确的阳离子-π 相互作用能，用于经验公式化和参数化。然后，基于基准计算构建经验方程并优化参数。阳离子-π 相互作用是距离和取向依赖性的。相应地，阳离子-π 相互作用的经验方程是两个变量 r 和 θ 的函数。提出了两种类型的阳离子-π 相互作用的经验方程。一种是改进的距离和取向依赖性 Lennard-Jones 方程。另一种是两个变量 r 和 θ 的多项式函数。基于氨基酸的经验方程和参数为评估蛋白质相互作用中的阳离子-π 相互作用能提供了简单而有用的工具。
