title: High-throughput screening and quantitative structure-efficacy relationship models of potential displacer molecules for ion-exchange systems.
abstract: A technique is presented for the high-throughput screening of ion-exchange displacers. Potential displacers were employed to displace proteins in parallel batch ion-exchange experiments. The percentage of protein displaced from a particular stationary phase was then used as a parameter to rank the displacers. By employing this technique, a large number of molecules possessing a range of affinities and properties could be rapidly evaluated. This data was then used together with traditional and electron density-based transferable atom equivalent (TAE) molecular descriptors computed for the displacer molecules to produce quantitative structure-efficacy relationship (QSER) models using a genetic algorithm/partial least squares (GA/PLS) regression approach. The QSER models were generated using a portion of the protein-displacement data, with the remainder serving as a test set. Descriptor selection and model building was accomplished using a genetic algorithm/partial least squares approach. The resulting models were found to have high-correlation coefficients and could be used to accurately predict the behavior of molecules not included in the training set. In addition, the models were employed to examine a virtual library of displacers based on modifications of neomycin to provide further insight into displacer design. The results presented here indicate that it may be possible to design displacers that can dramatically improve the effective selectivity of ion-exchange chromatographic materials.
authors.affiliation: Department of Chemical Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, New York 12180, USA.
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Mazza
authors.forename: Kaushal
authors.initials: K
authors.lastname: Rege
authors.forename: Curt M
authors.initials: CM
authors.lastname: Breneman
authors.forename: N
authors.initials: N
authors.lastname: Sukumar
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
authors.forename: Steven M
authors.initials: SM
authors.lastname: Cramer
mesh_terms: D000465:Algorithms; D000818:Animals; D002645:Chickens; D002852:Chromatography, Ion Exchange / Q000295:instrumentation* / Q000379:methods*; D003198:Computer Simulation; D003574:Cytochrome c Group / Q000032:analysis; D004527:Egg Proteins / Q000032:analysis; D006736:Horses; D008958:Models, Molecular; D015335:Molecular Probes; D015394:Molecular Structure; D009113:Muramidase / Q000032:analysis; D009206:Myocardium / Q000201:enzymology; D011485:Protein Binding; D011506:Proteins / Q000032:analysis*; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012685:Sepharose; D013379:Substrate Specificity
chemical_list: D003574:Cytochrome c Group; D004527:Egg Proteins; D015335:Molecular Probes; D011506:Proteins; D012685:Sepharose; D009113:Muramidase