Preferential binding affinity of ions and their effect on structure and dynamics of water near antimicrobial peptide

Abstract

Water containing dissolved salts is often found to play important roles in many chemical and biological processes. They affect the stability of the amino acids and proteins by altering the liquid water structure. The formation of a mixture of non-uniform density regions in liquid water; commonly known as Low-density water and High-density water is a well-known fact experimentally; which lends uniqueness to the ubiquitous water. The behavior of these different types of water at the interface and the bulk region of the biomolecules around the hydrophobic and hydrophilic residues under the influence of different alkali metal ions, such as LiCl, NaCl, and KCl is an important unexplored question in understanding of many biomolecular processes. To address this, we carried out MD simulation of antimicrobial peptide (PDB ID: 5Z32) for two different model potentials (CHARMM-SPC/E and AMBER-TIP4P) and performed the structural analysis of water in terms of the radial distribution function, number of hydrogen bonds, orientation, tetrahedral order parameter, voids analysis to analyze the related dynamical properties like preferential binding affinity, diffusion, hydrogen bond dynamics, entropy. The water molecules around the hydrophilic environment are found to be more disruptive containing more broken hydrogen bonds in comparison to the hydrophobic environment. It is also found that the water molecules present near the protein surface are of low density and that near the bulk is of high density. This leads to the higher self-diffusion coefficient of the water molecules and less hydrogen bond lifetime at the bulk. The maximum difference is found for the solutions containing high charge density, Lithium ions. Lithium ions have a strong preferential binding affinity towards protein surface resulting in strong solvation shells containing more tetrahedral-like water structure which has low diffusion, low entropy, and higher hydrogen bond lifetime. The diffusion of the water molecules, however, increases towards the higher solvation shells. Potassium on the other hand has less preference to live on protein surfaces resulting in similar diffusion values in the bulk and interface water molecules. © 2021 Elsevier B.V.