Experimental Evidence of Solvent-Separated Ion Pairs as Metastable States in Electrostatic Interactions of Biological Macromolecules

J Phys Chem Lett. 2019 Dec 19;10(24):7937-7941. doi: 10.1021/acs.jpclett.9b03084. Epub 2019 Dec 11.

Abstract

Electrostatic interactions via ion pairs are vital for biological macromolecules. Regarding the free energy of each ion pair as a function of the interionic distance, continuum electrostatic models predict a single energy minimum corresponding to the contact ion-pair (CIP) state, whereas atomically detailed theoretical hydration studies predict multiple energy minima corresponding to the CIP and solvent-separated ion-pair (SIP) states. Through a statistical analysis of high-resolution crystal structures, we present experimental evidence of the SIP as a metastable state. The histogram of interionic distances between protein side-chain NH3+ and DNA phosphate groups clearly shows two major peaks corresponding to the CIP and SIP states. The statistical data are consistent with the probability distribution of the CIP-SIP equilibria previously obtained with molecular dynamics simulations. Spatial distributions of NH3+ ions and water molecules around phosphates reveal preferential sites for CIP and SIP formations and show how the ions compete with water molecules.

MeSH terms

  • Amines / chemistry
  • DNA / chemistry
  • Hydrogen Bonding
  • Ions / chemistry
  • Macromolecular Substances / chemistry*
  • Molecular Dynamics Simulation
  • Phosphates / chemistry
  • Protein Binding
  • Protein Conformation
  • Proteins / chemistry
  • Solvents / chemistry*
  • Static Electricity
  • Thermodynamics
  • Water

Substances

  • Amines
  • Ions
  • Macromolecular Substances
  • Phosphates
  • Proteins
  • Solvents
  • Water
  • DNA