Pinpointing dynamic coupling in enzymes for efficient drug design

Enzymes are proteins that catalyze almost every chemical reaction in living systems, achieving rate enhancements of up to 21 orders of magnitude relative to the uncatalyzed reactions. However, despite a century of intense investigation, the biophysical basis of the enormous catalytic power of enzymes is not completely understood. Enzymes are not only central to living systems, but also to many industrial processes such as the production of food, textiles, detergents, pharmaceuticals and other chemicals where environmentally friendly, green methods are of ever increasing importance. Because of their central role for life, enzymes are key drug targets and enzyme inhibition is a central strategy in the design of new drugs. Acetylsalicylic acid, azidothymidine, acyclovir, allopurinol, chloramphenicol, exemestane, fosfomycin, isoniazid, methotrexate, profens, proguanil, statins, thiouracil and warfarin are but a small subset of approved drug substances that are used in the clinic to treat, among others, pain, fever, inflammation, malaria, cancer, HIV, bacterial and viral infections, rheumatoid arthritis, osteoarthritis and heart disease, through the inhibition of key enzymes