背景:在生物分子结构和相互作用的研究中,极性氢键(Hp-π)是一种广泛的分子相互作用类型。在20个天然氨基酸中的蛋白质11和DNA(或RNA)中,所有四种核酸都参与了这种类型的相互作用。
结果:使用高水平QM方法CCSD/6-311G研究了蛋白质中的Hp-π(d,p)在真空和溶液(水,乙腈,和环己烷)。三种量子化学方法(B3LYP,CCSD,和CCSD(T))和三个基础集(6-311+G(d,P),TZVP,和cc-pVTZ)进行比较。Hp-π供体包括R2NH,RNH2,ROH,和C6H5OH;受体是芳香族氨基酸,肽键单元,和小的共轭π基团。四个氨基酸对的Hp-π相互作用能(Ser-Phe,Lys-Phe,His-Phe,和Tyr-Phe)进行定量计算。
结论:从计算结果中抽象出五个结论点。(1)常见的DFT方法B3LYP未能描述Hp-π相互作用。另一方面,CCSD/6-311+G(d,P)加上重影原子H-Bq可以产生更好的结果,非常接近最先进的方法CCSD(T)/cc-pVTZ。(2)Hp-π相互作用是指向π平面相互作用,拥有比其他相互作用类型更多的相互作用构象和更宽的能量范围,如常见的氢键和静电相互作用。(3)在蛋白质中,Hp-π相互作用能在10至30kJ/mol的范围内,与普通氢键相互作用相当甚至更大。(4)Hp-π相互作用的键长在垂直于π平面的方向上在2.30至3.00的范围内,比常见的氢键长得多(〜1.9µ)。(5)像常见的氢键相互作用,Hp-π相互作用受溶剂化效应的影响较小。
BACKGROUND: In the
study of biomolecular structures and interactions the polar hydrogen-π bonds (Hp-π) are an extensive molecular interaction type. In proteins 11 of 20 natural amino acids and in DNA (or RNA) all four nucleic acids are involved in this type interaction.
RESULTS: The Hp-π in proteins are studied using high level QM method CCSD/6-311 + G(d,p) + H-Bq (ghost hydrogen basis functions) in vacuum and in solutions (water, acetonitrile, and cyclohexane). Three quantum chemical methods (B3LYP, CCSD, and CCSD(T)) and three basis sets (6-311 + G(d,p), TZVP, and cc-pVTZ) are compared. The Hp-π donors include R2NH, RNH2, ROH, and C6H5OH; and the acceptors are aromatic amino acids, peptide bond unit, and small conjugate π-groups. The Hp-π interaction energies of four amino acid pairs (Ser-Phe, Lys-Phe, His-Phe, and Tyr-Phe) are quantitatively calculated.
CONCLUSIONS: Five conclusion points are abstracted from the calculation results. (1) The common DFT method B3LYP fails in describing the Hp-π interactions. On the other hand, CCSD/6-311 + G(d,p) plus ghost atom H-Bq can yield better results, very close to the state-of-the-art method CCSD(T)/cc-pVTZ. (2) The Hp-π interactions are point to π-plane interactions, possessing much more interaction conformations and broader energy range than other interaction types, such as common hydrogen bond and electrostatic interactions. (3) In proteins the Hp-π interaction energies are in the range 10 to 30 kJ/mol, comparable or even larger than common hydrogen bond interactions. (4) The bond length of Hp-π interactions are in the region from 2.30 to 3.00 Å at the perpendicular direction to the π-plane, much longer than the common hydrogen bonds (~1.9 Å). (5) Like common hydrogen bond interactions, the Hp-π interactions are less affected by solvation effects.