Protein Kinase Inhibitors Highlight the Complexities of Drug-Target Non-Covalent Interactions

Atomic resolution structures of drug targets enable drug discovery, but generally not by a simple programmatic process. A popular expectation is that a single target structure will reveal what is needed to block its pathogenic activity. In contrast, the practical experience of recent years shows how complexities at every stage of drug discovery processes challenge predictivity. This is true not only at the scale of the biological organism, but also at the atomic scale, with respect to the drug-target interactions. Fortunately, high throughput experimental methods and data mining techniques used in combination continue to revolutionize pharmaceutical research. This article illustrates how “structure based drug design” might rather be considered “structure assisted drug discovery” with examples taken from the major emerging class of anticancer drugs, protein kinase inhibitors.