Investigation of mobile phase salt type effects on protein retention and selectivity in cation-exchange systems using quantitative structure retention relationship models

Asif Ladiwala, Kaushal Rege, Curt M. Breneman, Steven M. Cramer

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

In this paper, the effect of the salt counterion on protein retention in cation-exchange systems is investigated using experimental data and quantitative structure retention relationship (QSRR) models. Linear gradient experiments were carried out in the presence of three displacing counterions (sodium, ammonium, and calcium) on two cation-exchange stationary phase materials (Fast Flow Sepharose SP and Source 15S). QSRR models based on a support vector machine regression approach were developed using the experimental chromatographic data in concert with molecular descriptors computed from protein crystal structures. The resulting QSRR models were well correlated (r2=0.8452-0.9599), and the predictive power of these models was demonstrated with proteins not included in the derivation of the models. The key descriptors reflected in the models were then used to evaluate the phenomena responsible for protein retention in the presence of different salt counterions. In addition to the standard competitive binding effects of the cations, the results indicated that retention also depends on the relative ability of the cations to shield charges on the protein as well as the increased importance of hydrophobic interactions in the presence of a strong kosmotrope such as Ca2+. This work provides insight into the behavior of proteins in cation-exchange systems in the presence of various salt counterions and offers an efficient tool for the a priori prediction of protein retention.

Original languageEnglish (US)
Pages (from-to)8443-8454
Number of pages12
JournalLangmuir
Volume19
Issue number20
DOIs
StatePublished - Sep 30 2003
Externally publishedYes

Fingerprint

Cations
Ion exchange
Salts
selectivity
Positive ions
salts
proteins
Proteins
cations
data structures
Ammonium Compounds
Support vector machines
regression analysis
calcium
Calcium
derivation
Crystal structure
Sodium
sodium
gradients

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

Cite this

Investigation of mobile phase salt type effects on protein retention and selectivity in cation-exchange systems using quantitative structure retention relationship models. / Ladiwala, Asif; Rege, Kaushal; Breneman, Curt M.; Cramer, Steven M.

In: Langmuir, Vol. 19, No. 20, 30.09.2003, p. 8443-8454.

Research output: Contribution to journalArticle

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