文献类型：期刊文献

英文题名：The Stabilization Effect of Dielectric Constant and Acidic Amino Acids on Arginine-Arginine (Arg-Arg) Pairings: Database Survey and Computational Studies

作者：Zhang, Zhengyan[1,2];Xu, Zhijian[2];Yang, Zhuo[2];Liu, Yingtao[2];Wang, Jin'an[2];Shao, Qiang[2];Li, Shujin[1];Lu, Yunxiang[3];Zhu, Weiliang[2]

机构：[1]Soochow Univ, Coll Chem Chem Engn & Mat Sci, Suzhou 215123, Jiangsu, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China;[3]E China Univ Sci & Technol, Dept Chem, Shanghai 200237, Peoples R China

年份：2013

卷号：117

期号：17

起止页码：4827

外文期刊名：JOURNAL OF PHYSICAL CHEMISTRY B

收录：;EI(收录号：20131916318447);WOS:【SCI-EXPANDED(收录号:WOS:000318536700011)】；

基金：This research was supported by the Ministry of Science and Technology (2012AA01A305), National Major Project (2012ZX09301001-004), National Natural Science Foundation (81273435, 20977064, 21103047, 91013008, and 21021063) and the priority academic program development of Jiangsu higher education institutions.

语种：英文

外文关键词：Density functional theory - Computation theory - Design for testability - Proteins - Surveys - Molecules

摘要：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 center dot center dot center dot carbon (CZ center dot center dot center dot CZ). interaction distance less than 5 A. 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 poring 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.