Proposing the Promiscuous Protein Structures in JNK1 and JNK3 for Virtual Screening in Pursuit of Potential Leads.

Over the past decade, the available crystal structures have almost doubled in Protein Data Bank (PDB) providing the research community with a series of similar crystal structures to choose from for future docking studies. With the steady growth in the number of high-resolution three-dimensional protein structures, ligand docking-based virtual screening of chemical libraries to a receptor plays a critical role in the drug discovery process by identifying new drug candidates. Thus, identifying potential candidates among all the available structures in a database for docking studies is of utmost importance. Our work examined whether one could use the resolution of a number of known structures, without considering other parameters, to choose a good experimental structure for various docking studies to find more useful drug leads. We expected that a good experimental structure for docking studies to be the one that gave favorable docking with the largest number of ligands among the experimental structures to be selected. We chose three protein test systems for our study, all belonging to the family of MAPK: (1) JNK1, (2) JNK2, and (3) JNK3. On analysis of the results, the best resolution structures showed significant variations from the expected values in their result, whereas the poor resolution structures proved to be better candidates for docking studies.