How to design a drug for the disordered proteins?

•Protein structural disorders make drug design difficult.•Equilibrium fluctuations of protein can be used as insight for drug design.•Noncanonical amino acids can be used for molecule design.•The elusive IDPs and IDRs can become drug designable by employing these methods.

Structural disorders of proteins make drug design a difficult task. The gel-like state of intrinsically disordered protein (IDP) or intrinsically disordered regions (IDRs) remains a big puzzle for drug designers. Here, we propose a novel concept for drug design by understanding protein disintegration and protein–protein interaction (PPI) using molecular dynamics (MD) simulation and propose a possible approach for overcoming current obstacles in IDP drug design.