Peptide capture agents are stable and robust alternatives to antibodies that have become increasingly useful tools for a variety of sensing applications. These recognition elements can be rapidly and reliably isolated by semi-automated biopanning of bacterial display libraries, but binding specificity remains a primary concern. For a chosen pair of structurally similar proteins, abrax and RiVax, with significant homology and comparable function, we have discovered peptides and consensus families which are selective for one similar protein over the other. We have teamed experimental analysis of on-cell peptide binding affinity and specificity using Fluorescence Activated Cell Sorting (FACS) with bioinformatic analysis of sequences and molecular modeling of binding location using the XPairIt peptide-protein docking protocol to better understand what is driving the selectivity. In addition to peptide binding location predictions, differences in binding pocket size and pocket environment, including local hydrophobicity and electronegativity, were noted. This model system demonstrates that peptide capture candidates can be quite selective without further maturation, even in a structurally similar protein system. The <i>in silico</i> method of analysis employed is used to down-select candidates for further maturation.<br/>

Coupling experiment and modeling to understand peptide capture agent specificity for similar protein targets

253rd National Meeting (2017)

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