Incorporation of Hard and Soft Protein-Protein Interactions into Models for Crowding Effects in Binary and Ternary Protein Mixtures. Comparison of Approximate Analytical Solutions with Numerical Simulation

J Phys Chem B. 2016 Nov 23;120(46):11866-11872. doi: 10.1021/acs.jpcb.6b07736. Epub 2016 Nov 15.

Abstract

In order to better understand how nonspecific interactions between solutes can modulate specific biochemical reactions taking place in complex media, we introduce a simplified model aimed at elucidating general principles. In this model, solutions containing two or three species of interacting globular proteins are modeled as a fluid of spherical particles interacting through square well potentials that qualitatively capture both steric hard core repulsion and longer-ranged attraction or repulsion. The excess chemical potential, or free energy of solvation, of each particle species is calculated as a function of species concentrations, particle radii, and square well interaction range and depth. The results of analytical models incorporating two-body and three-body interactions are compared with the estimates of free energy obtained via Widom insertion into simulated equilibrium square-well fluids. The analytical models agree well with results of numeric simulations carried out for a variety of model parameters and fluid compositions up to a total particle volume fraction of ca. 0.2.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Molecular Dynamics Simulation*
  • Protein Binding
  • Proteins / chemistry*
  • Solutions
  • Thermodynamics

Substances

  • Proteins
  • Solutions