A square peg doesn’t fit a round hole. But what if the peg could change the shape of the hole? A newly developed drug molecule can do something surprisingly similar when binding to its target protein, according to a University at Buffalo-led study published Tuesday (Sept. 15) in Angewandte Chemie International Edition.

The molecule, an inhibitor designed to block activity, initially clashed with a flexible loop in the structure of a protein implicated in cancer and known as p38 delta. This clash would normally hinder binding, but it instead caused the loop to change shape and wrap around the molecule, creating an unusually snug fit.

The molecule represented a 12,000-fold improvement in selectivity for p38 delta and was 110-fold more potent than previously available compounds.