Élucidation et caractérisation fonctionnelle de nouveaux sites d'inhibition allostérique chez des enzymes à fort potentiel thérapeutique


Nicolas Doucet

Institut national de la recherche scientifique (INRS)


Domaine : Maladies infectieuses et immunitaires

Programme chercheurs-boursiers - Junior 2

Concours 2016-2017



The mutation or molecular dysfunction of proteins and enzymes in human cells are the cause of many diseases, ranging from cancer to degenerative pathologies, in addition to antibiotic resistance observed among the bacteria infecting us. The vast majority of commercial drugs currently on the market are small molecules whose action is to bind the active site of a protein or enzyme to inhibit or disrupt its function on the surface or inside our cells. However, several proteins or enzymes in our body are often very similar in their active sites, resulting in non-specific drug binding to many molecular targets. This can obviously cause unwanted or even dangerous side effects. Resistance also appears in the active site of certain enzymes, resulting in ineffective medicines that no longer bind and inhibit their target.

Our research aims to elucidate the existence of new "dynamic" active sites on the surface of proteins and enzymes showing high therapeutic potential. These sites were previously unknown because they are based on recent discoveries showing that the molecular movements of proteins and enzymes are organized, non-random and essential to their biological function. We use experimental methods to elucidate and characterize their atomic motions, offering an alternative method to inhibit or control protein function using new drugs that target these new sites. We apply this unique methodology to the study of many clinically relevant systems, particularly focusing on cancer and bacterial antibiotic resistance.