Where proteins are concerned, the relationship between structure and function is more complicated than previously thought. A team of researchers, led by Zachary Wood at the University of Georgia, Athens, has shown that disordered bits of proteins, often assumed to have no functional role, can fine-tune a protein’s entropy and function (Nature2018, DOI: 10.1038/s41586-018-0699-5). Proteins aren’t made of just structural elements like α-helices and β-sheets. More than 40% of the human proteome contains wobbly sections that don’t have a stable structure, known as intrinsically disordered regions. One such wobbly region is found at the end of the protein that forms the human dehydrogenase enzyme UGDH. Wood’s team showed that deleting these long tails changes the binding affinity of the enzyme for its inhibitor. Additional experiments showed that it is not the sequence but the length of the disordered tail that matters. The tail adds entropy and thus changes the energy landscape of the protein. Entropic fine tuning, the scientists conclude, might explain why there are so many disordered regions in the proteome.