Thermodynamics of Ion Pair Formations Between Charged Poly(Amino Acid)s

Abstract

Electrostatic interactions between the positively and negatively charged amino acids in proteins play an important role in macromolecular stability, binding, and recognition. Numerous amino acids in proteins are ionizable and may exist in negatively (e.g., Glu, Asp, Cys, Tyr) or positively (e.g., Arg, Lys, His, Orn) charged form dependent on pH and their pKas. In this work, isothermal titration calorimetry was used to determine the average standard values of thermodynamic parameters (the Gibbs free energy, enthalpy, entropy, and the heat capacity) of interaction between the positively charged amino acid homopolymers (polyarginine, polylysine, and polyornithine) and the negatively charged homopolymers (polyaspartic and polyglutamic acids). These values are of potential use in the computational models of interacting proteins and other biological macromolecules. The study showed that oppositely charged poly(amino acid)s bound each other with the stoichiometry of one positive to one negative charge. Arginine bound to the negatively charged amino acids with exothermic enthalpy and higher affinity than lysine. This result also suggests that positive charges in proteins should not be considered entirely equivalent if carried by lysine or arginine. The difference in binding energy of arginine and lysine association with the negatively charged amino acids was attributed to the enthalpy of the second ionic hydrogen bond formation between the guanidine and carboxylic groups. Despite the favorable enthalpic contribution, all such ion pair formation reactions were largely entropy-driven. Consistent with previously observed ionic interactions, the positive heat capacity was always observed during the amino acid ion pair formation.

Charge‐mediated proteasome targeting

“…Thus, arginine binds negatively charged amino acids at least 100-fold more strongly than lysine, with resulting DG 10 kcal/mol and binding constant K b . 10 7 (46). We therefore suggest that arginine residues, rather than lysine residues, are main anchors, fastening MBP to proteasome, whereas alanine, glycine, and serine provide flexibility of the main chain.…”

Arginine prevents thermal aggregation of hen egg white proteins

“…Protein aggregation is generally prevented by the additive that can interact with the protein surface. The molecular mechanism how Arg interacts with HEWP and prevents the thermal aggregation of HEWP as a solvent additive could be briefly summarized as follows (Shiraki et al, 2016): (i) Arg prevents the chemical modification of protein such as deamidation of side chains of Asparagine and Glutamine (Tomita, Nagasaki, & Shiraki, 2012;; (ii) Arg causes steric hindrance by sandwiched between proteins, so called gap effect (Baynes, Wang, & Trout, 2005;Shukla & Trout, 2010;Vagenende, Han, Mueller, & Trout, 2013); (iii) Arg interacts with proteins by specific interactions, such as cation-π interactions, electrostatic interactions, hydrophobic interactions, and hydrogen bonding (Petrauskas, Maximowitsch, & Matulis, 2015;Shah, Shaikh, Peng, & Rajagopalan, 2011); (iv) Arg increases the surface tension of water. This results in the inhibition of protein aggregation as a solvent effect (Arakawa et al, 2007;Arakawa & Timasheff, 1983); and finally (v) Arg is one of the salts in aqueous solution at neutral pH (Inoue et al, 2014a).…”

Designing interactions by control of protein–ligand complex conformation: tuning arginine–arene interaction geometry for enhanced electrostatic protein–ligand interactions

“…, the guanidine and sulfate groups) is entirely due to favourable entropy and involves unfavourable enthalpy. 27 , 28 We note that the sulfate group of 19 had a much greater influence on both enthalpy and entropy than did the sulfate group of 20 . However, analyzing the change in binding free energy (ΔΔ G ) upon introduction of a 2- O -sulfate to give structures 16 and 20 , it is clear that the 2- O -sulfate group of 20 achieves a higher gain in free energy than the 2- O -sulfate group of 19 .…”

“…However, analyzing the change in binding free energy (ΔΔ G ) upon introduction of a 2- O -sulfate to give structures 16 and 20 , it is clear that the 2- O -sulfate group of 20 achieves a higher gain in free energy than the 2- O -sulfate group of 19 . A useful point of reference is the ratio ΔΔ S /ΔΔ H , 27 , 28 which should be close to 1.35ΔΔ G /(–0.35ΔΔ G ) = –3.85 in the hypothetical case that ΔΔ G is caused entirely by electrostatic interactions. We find that ΔΔ S /ΔΔ H = –1.3 for the comparison of 20 vs. 16 , while ΔΔ S /ΔΔ H = –1.0 for the comparison of 19 vs. 15 , thus suggesting that electrostatic effects play a greater role in 20 than in 19 , as expected from the crystal structures.…”