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Amino acid side chain interactions in the presence of salts - PubMed

  • ️Sat Jan 01 2005

Amino acid side chain interactions in the presence of salts

Sergio A Hassan. J Phys Chem B. 2005.

Abstract

The effects of salt on the intermolecular interactions between polar/charged amino acids are investigated through molecular dynamics simulations. The mean forces and associated potentials are calculated for NaCl salt in the 0-2 M concentration range at 298 K. It is found that the addition of salt may stabilize or destabilize the interactions, depending on the nature of the interacting molecules. The degree of (de)stabilization is quantified, and the origin of the salt-dependent modulation is discussed based upon an analysis of solvent density profiles. To gain insight into the molecular origin of the salt modulation, spatial distribution functions (sdf's) are calculated, revealing a high degree of solvent structuredness in all cases. The peaks in the sdf's are consistent with long-range hydrogen-bonding networks connecting the solute hydrophilic groups, and that contribute to their intermolecular solvent-induced forces. The restructuring of water around the solutes as they dissociate from close contact is analyzed. This analysis offers clues on how the solvent structure modulates the effective intermolecular interactions in complex solutes. This modulation results from a critical balance between bulk electrostatic forces and those exerted by (i) the water molecules in the structured region between the monomers, which is disrupted by ions that transiently enter the hydration shells, and (ii) the ions in the hydration shells in direct interactions with the solutes. The implications of these findings in protein/ligand (noncovalent) association/dissociation mechanisms are briefly discussed.

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Figures

Figure 1
Figure 1

(A) Potentials of mean force (VM, in kcal/mol) for the Asp− –Arg+ dimer as a function of the intermolecular (PA = proton–acceptor, in Å) distance, at different NaCl salt concentrations. Inset: Changes of the potentials at the contact (cm), transition state (ts), and solvent-separated (ss) distances as a function of [NaCl]. (B) Changes (ΔV2) of the potentials at 2 M salt concentration with respect to the salt-free solvent. Arrows (a, b, and c) mark the approximate intermolecular distances where changes of the PMF occur; these changes coincide with the development of new solvent density maxima in the space between the monomers (see text and Figure 6). Inset: Solvent mean force (Fs,M, in kcal/mol/Å) for pure water and 2 M solution. (C) Bulk (electrostatics) and nonbulk (solvation-shell) contributions to the PMF as a function of the intermolecular distance, in pure water and 2 M salt concentration.

Figure 2
Figure 2

As in Figures 1A and 1B for Ser–Arg+ (see Figure 7).

Figure 3
Figure 3

As in Figures 1A and 1B for Asp− –Ser (see Figure 8).

Figure 4
Figure 4

As in Figures 1A and 1B for Ser–Arg+ (see Figure 7).

Figure 5
Figure 5

Changes (ΔVM) of the PMF (in kcal/mol) at the contact distance (rcm) as a function of [NaCl] (in M) for the eight dimers studied. The reference is pure water (error bars estimated as σΔVM(r) ≈ σV0(r) + σVM(r)); negative values indicate stabilization of the dimer at the corresponding value of [NaCl].

Figure 6
Figure 6

Peaks in the spatial distribution functions (sdf’s) of pure water at three intermolecular distances: r = rss = 4.6 Å (upper panel; arrow a in Figure 1B), r = 7.5 Å (middle), and r = 10 Å (lower). Peaks connecting the side chains functional groups are labeled (m) in decreasing order of gm(r) (see text): upper panel, g1 = 3.7; middle panel, g1 = 3.2, g2 = 3.0, g3 = 2.7; lower panel, g1 = 2.7, g2 = 1.9, g3 = 1.7 (error bars estimated as σ [gm] ≈ 0.2 in all cases). Only heavy atoms and polar hydrogens are displayed.

Figure 7
Figure 7

As in Figure 6 for Ser–Arg+: upper panel, g1 = 3.4; middle panel, g1 = 3.5, g2 = 2.8; lower panel, g1 = 3.0, g2 = 2.8, g3 = 1.6.

Figure 8
Figure 8

As in Figure 6 for Asp− –Ser: upper panel, g1 = 3.8; lower, g1 = 3.0, g2 = 2.4.

Figure 9
Figure 9

As in Figure 6 for Ser–Ser: upper panel, g1 = 3.8; lower panel, g1 = 3.6, g2 = 2.7.

Figure 10
Figure 10

As in Figure 1B for Asp− –Lys+.

Figure 11
Figure 11

Spatial distribution functions (sdf’s) of ions (red, Cl−; blue, Na+) around Asp− –Arg+ (upper panel) and Asp− –Lys+ (lower panel) at an intermolecular separation r = 7 Å (see Figures 1B and 10).

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