The protein interactions in protein-ligand binding and protein-protein interfaces can be regarded based on structural similarity of the secondary structure elements.  The most prominent example is the protein fold of a protein domain that is more conserved than the amino acid sequence. Proteins with similar fold but dissimilar sequence and function can bind similar ligands and interact with similar proteins. The next level corresponds to the spatial arrangement of the secondary structure elements around the ligand binding site ('ligand-sensing cores') or in the protein interface ('interface-sensing surfaces'). These similarities in otherwise unrelated proteins can be useful in predicting drug polypharmacology.  The successful applications in drug design using predicted polypharmacology in protein-ligand binding will be shown and the analogy in the design of protein-protein interface inhibitors and the potential of polypharmacology prediction will be discussed.Reference: Koch, O. Future Med. Chem. 2011; 3(6): 699-708.

Predicting drug polypharmacology using secondary structure element information

243rd National Meeting (2012)

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