title: Theoretical study on the polar hydrogen-π (Hp-π) interactions between protein side chains.
abstract: 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.
authors.affiliation: State Key Laboratory of Non-food Biomass and Enzyme Technology, National Engineering Research Center for Non-food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, Guangxi 530007, China ; Gordon Life Science Institute, San Diego, CA 92130, USA.
authors.forename: Qi-Shi
authors.initials: QS
authors.lastname: Du
authors.affiliation: State Key Laboratory of Non-food Biomass and Enzyme Technology, National Engineering Research Center for Non-food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, Guangxi 530007, China ; Life Science and Biotechnology College, Guangxi University, Nanning, Guangxi, 530004, China.
authors.forename: Qing-Yan
authors.initials: QY
authors.lastname: Wang
authors.affiliation: Life Science and Biotechnology College, Guangxi University, Nanning, Guangxi, 530004, China.
authors.forename: Li-Qin
authors.initials: LQ
authors.lastname: Du
authors.affiliation: State Key Laboratory of Non-food Biomass and Enzyme Technology, National Engineering Research Center for Non-food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, Guangxi 530007, China ; Life Science and Biotechnology College, Guangxi University, Nanning, Guangxi, 530004, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Non-food Biomass and Enzyme Technology, National Engineering Research Center for Non-food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning, Guangxi 530007, China ; Life Science and Biotechnology College, Guangxi University, Nanning, Guangxi, 530004, China.
authors.forename: Ri-Bo
authors.initials: RB
authors.lastname: Huang
keywords: CCSD; Ghost atom; Hydrogen-π interactions; Molecular interactions; Protein backbones; Protein structures