Predicting the activity coefficients of free-solvent for concentrated globular protein solutions using independently determined physical parameters

PLoS One. 2013 Dec 4;8(12):e81933. doi: 10.1371/journal.pone.0081933. eCollection 2013.

Abstract

The activity coefficient is largely considered an empirical parameter that was traditionally introduced to correct the non-ideality observed in thermodynamic systems such as osmotic pressure. Here, the activity coefficient of free-solvent is related to physically realistic parameters and a mathematical expression is developed to directly predict the activity coefficients of free-solvent, for aqueous protein solutions up to near-saturation concentrations. The model is based on the free-solvent model, which has previously been shown to provide excellent prediction of the osmotic pressure of concentrated and crowded globular proteins in aqueous solutions up to near-saturation concentrations. Thus, this model uses only the independently determined, physically realizable quantities: mole fraction, solvent accessible surface area, and ion binding, in its prediction. Predictions are presented for the activity coefficients of free-solvent for near-saturated protein solutions containing either bovine serum albumin or hemoglobin. As a verification step, the predictability of the model for the activity coefficient of sucrose solutions was evaluated. The predicted activity coefficients of free-solvent are compared to the calculated activity coefficients of free-solvent based on osmotic pressure data. It is observed that the predicted activity coefficients are increasingly dependent on the solute-solvent parameters as the protein concentration increases to near-saturation concentrations.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Chemical Phenomena*
  • Hemoglobins / chemistry*
  • Hydrogen-Ion Concentration
  • Serum Albumin, Bovine / chemistry*
  • Sheep
  • Solutions
  • Solvents / chemistry*
  • Sucrose / chemistry

Substances

  • Hemoglobins
  • Solutions
  • Solvents
  • Serum Albumin, Bovine
  • Sucrose

Grants and funding

Devin W. McBride was supported by the National Science Foundation (NSF) IGERT Video Bioinformatics Training Grant and was supported by an NSF IGERT Video Bioinformatics Fellowship (grant number DGE 0903667). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.