title: Prediction of protein retention times in hydrophobic interaction chromatography by robust statistical characterization of their atomic-level surface properties.
abstract: 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. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:372-381, 2016.
authors.affiliation: Dept. of Biotechnology, TU Delft, Julianalaan 67, Delft, 2628 BC, The Netherlands.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Hanke
authors.affiliation: Dept. of Biotechnology, TU Delft, Julianalaan 67, Delft, 2628 BC, The Netherlands.
authors.forename: Marieke E
authors.initials: ME
authors.lastname: Klijn
authors.affiliation: Dept. of Biotechnology, TU Delft, Julianalaan 67, Delft, 2628 BC, The Netherlands.
authors.forename: Peter D E M
authors.initials: PD
authors.lastname: Verhaert
authors.affiliation: Dept. of Biotechnology, TU Delft, Julianalaan 67, Delft, 2628 BC, The Netherlands.
authors.forename: Luuk A M
authors.initials: LA
authors.lastname: van der Wielen
authors.affiliation: Dept. of Biotechnology, TU Delft, Julianalaan 67, Delft, 2628 BC, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Ottens
authors.affiliation: Synthon Biopharmaceuticals B.V, Microweg 22, GN, Nijmegen, 6503, The Netherlands.
authors.forename: Michel H M
authors.initials: MH
authors.lastname: Eppink
authors.affiliation: DSM Biotechnology Center, Alexander Fleminglaan 1, AX, Delft, 2613, The Netherlands.
authors.forename: Emile J A X
authors.initials: EJ
authors.lastname: van de Sandt
mesh_terms: D002845:Chromatography; D057927:Hydrophobic and Hydrophilic Interactions; D015233:Models, Statistical; D010316:Particle Size; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013499:Surface Properties; D013997:Time Factors
chemical_list: D011506:Proteins
keywords: atomic-level surface description; hydrophobic interaction chromatography; protein surface properties; retention time prediction; robust statistics