Machine Learning Model for Biomimetic Chromatography Peptide Ligands

Purification is an essential part of antibody production, which are important therapeutic biomolecules. Common methods of antibody purification rely on affinity chromatography (AC), wherein whole proteins are oftentimes used as ligands to catch the antibodies to be purified. While AC has been successful in purifying antibodies, it is associated with multiple challenges such as high cost and low stability, among others. A promising alternative is using short peptide sequences in place of whole proteins as the stationary phase for the chromatographic separation of the antibodies. In an effort to accelerate the discovery and development of short peptides for biomimetic chromatography, this study reports the creation of a machine learning classification which was trained and tested on 480 tetrapeptides. The optimized logistic regression model uses Cruciani properties as the input variables and can categorize peptides into one of two classes based on their binding affinity with immunoglobulin G (IgG). The externally validated model demonstrates satisfactory predictive performance and excellent discrimination as demonstrated by performance metrics such as AUC = 0.874, Balanced Accuracy = 0.874, F1 = 0.871, Precision = 0.884, and Recall = 0.859. Apart from this, the classifier has also provided valuable insights into important variables that influence the classification, such as electrostatic and hydrophobic interactions. Overall, the classifier can be regarded as a welcome development for biomimetic chromatography and is the first study that aims to integrate machine learning in the biomimetic chromatography peptide development process.