Predicting and Comparing Binding Affinities from OppA X-ray Crystal and Docked Structures
Date of Award
Master of Science (MS)
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.
Alhujayri, Marwah, "Predicting and Comparing Binding Affinities from OppA X-ray Crystal and Docked Structures" (2017). Chemistry Master’s Theses. 48.