Quantification of the effects of ionic strength, viscosity, and hydrophobicity on protein-ligand binding affinity

Christos P. Papaneophytou, Asterios I. Grigoroudis, Campbell McInnes, George Kontopidis

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

In order to quantify the interactions between molecules of biological interest, the determination of the dissociation constant (Kd) is essential. Estimation of the binding affinity in this way is routinely performed in "favorable" conditions for macromolecules. Crucial data for ligand-protein binding elucidation is mainly derived from techniques (e.g., macromolecular crystallography) that require the addition of high concentration of salts and/or other additives. In this study we have evaluated the effect of temperature, ionic strength, viscosity, and hydrophobicity on the Kd of three previously characterized protein-ligand systems, based on variation in their binding sites, in order to provide insight into how these often overlooked unconventional circumstances impact binding affinity. Our conclusions are as follows: (1) increasing solvent viscosity in general is detrimental to ligand binding, (2) moderate increases in temperature have marginal effects on the dissociation constant, and (3) the degree of hydrophobicity of the ligand and the binding site determines the extent of the influence of cosolvents and salt concentration on ligand binding affinity.

Original languageEnglish
Pages (from-to)931-936
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume5
Issue number8
DOIs
Publication statusPublished - 14 Aug 2014

Keywords

  • Affinity
  • dissociation constant
  • fluorescence spectroscopy
  • ion strength
  • solvent
  • viscosity

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