title: The stabilization effect of dielectric constant and acidic amino acids on arginine-arginine (Arg-Arg) pairings: database survey and computational studies.
abstract: Database survey in this study revealed that about one-third of the protein structures deposited in the Protein Data Bank (PDB) contain arginine-arginine (Arg-Arg) pairing with a carbon···carbon (CZ···CZ) interaction distance less than 5 Å. All the Arg-Arg pairings were found to bury in a polar environment composed of acidic residues, water molecules, and strong polarizable or negatively charged moieties from binding site or bound ligand. Most of the Arg-Arg pairings are solvent exposed and 68.3% Arg-Arg pairings are stabilized by acidic residues, forming Arg-Arg-Asp/Glu clusters. Density functional theory (DFT) was then employed to study the effect of environment on the pairing structures. It was revealed that Arg-Arg pairings become thermodynamically stable (about -1 kcal/mol) as the dielectric constant increases to 46.8 (DMSO), in good agreement with the results of the PDB survey. DFT calculations also demonstrated that perpendicular Arg-Arg pairing structures are favorable in low dielectric constant environment, while in high dielectric constant environment parallel structures are favorable. Additionally, the acidic residues can stabilize the Arg-Arg pairing structures to a large degree. Energy decomposition analysis of Arg-Arg pairings and Arg-Arg-Asp/Glu clusters showed that both solvation and electrostatic energies contribute significantly to their stability. The results reported herein should be very helpful for understanding Arg-Arg pairing and its application in drug design.
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science of Soochow University, Soochow University, Suzhou, Jiangsu, 215123, China.
authors.forename: Zhengyan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xu
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
authors.forename: Yingtao
authors.initials: Y
authors.lastname: Liu
authors.forename: Jin'an
authors.initials: J
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shao
authors.forename: Shujin
authors.initials: S
authors.lastname: Li
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Lu
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
mesh_terms: D024342:Amino Acids, Acidic / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D019295:Computational Biology; D030562:Databases, Protein; D004151:Dipeptides / Q000737:chemistry* / Q000378:metabolism; D018698:Glutamic Acid / Q000737:chemistry; D007700:Kinetics; D012997:Solvents / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D024342:Amino Acids, Acidic; D004151:Dipeptides; D012997:Solvents; C076685:arginylarginine; D001224:Aspartic Acid; D018698:Glutamic Acid; D002244:Carbon