The approach of exploiting highly conserved protein folds and structure in understanding protein function and in designing drugs leads to drugs that are less selective due to association with similar proteins. Over the years an open problem for researchers has been to develop drug design models based on non-conserved features to have higher selectivity. In recent times, a new structural feature, dehydron, has been investigated to vary across proteins with conserved folds. The importance of dehydron wrapping in ligand binding and its non-conservation across similar proteins makes it an important candidate as a marker in drug design. A series of proteins - PDB entries: 1IA8, 1NVQ, 1NVS, 1NVR, 1OKZ, and 1PKD - revealed the impact of dehydron wrapping on binding affinity of the ligands. Unlike other cases, inhibitor UCN in 1NVQ wrapped both the dehydrons in active site region of the checkpoint protein kinase, thereby showing an increased potency and higher selectivity. On detailed analysis of 193 protein kinases, roughly 70% were found to have two or more dehydrons in the neighborhood of the bound ligand. However, only around 20% of ligands actually wrapped two or more of these neighboring dehydrons. More than 70% of proteins had dehydrons within the active site region. These statistics clearly illustrate the significance of dehydrons and its potential use as a marker for drug design to enhance drug efficacy as well as selectivity, and to reduce side effects in the process
