Predicting and Comparing Binding Affinities from OppA X-ray Crystal and Docked Structures

Date of Award


Degree Type


Degree Name

Master of Science (MS)



First Advisor

Joseph Audie, Ph.D.


The present research sought to predict the binding affinity values for the crystal and the docked structures of twenty different protein-peptide interactions. In particular, the research involved studying the binding of twenty different tripeptides with the sequence motif K-X-K, where X is one of the twenty common amino acids, to the bacterial OppA protein using the PRODIGY binding free energy prediction method. PRODIGY was used to predict OppA-peptide binding affinities from high resolution x-ray structures and from high quality docked structures. All predictions were compared with experimental binding free energies determined using isothermal titration calorimetry (ITC). Correlation analysis revealed insignificant correlations for all PRODIGY predictions. Even sub-population analyses of hydrophobic, polar and charged tripeptide ligands failed to produce significant correlations. Hence, it is concluded that the PRODIGY method must be improved before it can be used to predict and explain binding affinities for OppA-peptide binding reactions.


Master's thesis submitted to the faculty of Sacred Heart University's Chemistry Program in partial fulfillment of the requirements for the degree of Master of Chemistry.