Importance of Rigidity in Designing Small Molecule Drugs To Tackle Protein–Protein Interactions (PPIs) through Stabilization of Desired Conformers: Miniperspective

Tackling PPIs, particularly by stabilizing clinically favored conformations of target proteins, with orally available, bona fide small molecules remains a significant but immensely worthwhile challenge for the pharmaceutical industry. Success may be more likely through the application of nature’s learnings to build intrinsic rigidity into the design of clinical candidates.