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.