The Stabilization Effect of Dielectric Constant and Acidic Amino Acids on Arginine鈥揂rginine (Arg鈥揂rg) Pairings: Database Survey and Computational Studies

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• 作者：Zhengyan Zhang ; Zhijian Xu ; Zhuo Yang ; Yingtao Liu ; Jin鈥檃n Wang ; Qiang Shao ; Shujin Li ; Yunxiang Lu ; Weiliang Zhu
• 刊名：The Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：May 2, 2013
• 年：2013
• 卷：117
• 期：17
• 页码：4827-4835
• 全文大小：509K
• 年卷期：v.117,no.17(May 2, 2013)
• ISSN：1520-5207

文摘

Database survey in this study revealed that about one-third of the protein structures deposited in the Protein Data Bank (PDB) contain arginine鈥揳rginine (Arg鈥揂rg) pairing with a carbon路路路carbon (CZ路路路CZ) interaction distance less than 5 脜. All the Arg鈥揂rg 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鈥揂rg pairings are solvent exposed and 68.3% Arg鈥揂rg pairings are stabilized by acidic residues, forming Arg鈥揂rg鈥揂sp/Glu clusters. Density functional theory (DFT) was then employed to study the effect of environment on the pairing structures. It was revealed that Arg鈥揂rg pairings become thermodynamically stable (about 鈭? 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鈥揂rg 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鈥揂rg pairing structures to a large degree. Energy decomposition analysis of Arg鈥揂rg pairings and Arg鈥揂rg鈥揂sp/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鈥揂rg pairing and its application in drug design.