TY - JOUR
T1 - Prediction of protein retention times in hydrophobic interaction chromatography by robust statistical characterization of their atomic-level surface properties
AU - Hanke, Alexander T.
AU - Klijn, Marieke E.
AU - Verhaert, Peter D.E.M.
AU - van der Wielen, Luuk A.M.
AU - Ottens, Marcel
AU - Eppink, Michel H.M.
AU - van de Sandt, Emile J.A.X.
N1 - Publisher Copyright:
© 2016 American Institute of Chemical Engineers Biotechnol.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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 (R2=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.
AB - 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 (R2=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.
KW - Atomic-level surface description
KW - Hydrophobic interaction chromatography
KW - Protein surface properties
KW - Retention time prediction
KW - Robust statistics
UR - http://www.scopus.com/inward/record.url?scp=84954556945&partnerID=8YFLogxK
U2 - 10.1002/btpr.2219
DO - 10.1002/btpr.2219
M3 - Article
C2 - 26698169
AN - SCOPUS:84954556945
SN - 8756-7938
VL - 32
SP - 372
EP - 381
JO - Biotechnology Progress
JF - Biotechnology Progress
IS - 2
ER -