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Prediction of protein retention times in hydrophobic interaction chromatography by robust statistical characterization of their atomic‐level surface properties
Author(s) -
Hanke Alexander T.,
Klijn Marieke E.,
Verhaert Peter D. E. M.,
van der Wielen Luuk A. M.,
Ottens Marcel,
Eppink Michel H. M.,
van de Sandt Emile J. A. X.
Publication year - 2016
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.2219
Subject(s) - dimensionless quantity , hydrophilic interaction chromatography , ternary operation , globular protein , characterization (materials science) , chemistry , chromatography , biological system , hydrophobic effect , surface (topology) , sensitivity (control systems) , accessible surface area , mathematics , crystallography , materials science , high performance liquid chromatography , computational chemistry , physics , computer science , thermodynamics , nanotechnology , organic chemistry , geometry , biology , electronic engineering , engineering , programming language
The correlation between the dimensionless retention times (DRT) of proteins in hydrophobic interaction chromatography (HIC) and their surface properties were investigated. A ternary atomic‐level hydrophobicity scale was used to calculate the distribution of local average hydrophobicity across the proteins surfaces. These distributions were characterized by robust descriptive statistics to reduce their sensitivity to small changes in the three‐dimensional structure. The applicability of these statistics for the prediction of protein retention behaviour was looked into. A linear combination of robust statistics describing the central tendency, heterogeneity and frequency of highly hydrophobic clusters was found to have a good predictive capability ( R 2 = 0.78), when combined a factor to account for protein size differences. The achieved error of prediction was 35% lower than for a similar model based on a description of the protein surface on an amino acid level. This indicates that a robust and mathematically simple model based on an atomic description of the protein surface can be used for the prediction of the retention behaviour of conformationally stable globular proteins with a well determined 3D structure in HIC. © 2016 American Institute of Chemical Engineers Biotechnol. Prog. , 32:372–381, 2016