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.