Taming molecular flexibility to tackle rare diseases.

摘要: Many mutations responsible of Fabry disease destabilize lysosomal alpha-galactosidase, but retain the enzymatic activity. These are associated to a milder phenotype and potentially curable with pharmacological therapy either chaperones or drugs that modulate proteostasis. We demonstrate effectiveness molecular dynamics simulations correlate genotype severity disease. studied relation between protein flexibility residual activity pathological missense mutants in cell. found occurring at flexible sites likely in vivo. The usefulness for diagnostic purposes is not limited galactosidase because destabilizing widely encountered other proteins, too, represent large share all ones human diseases.