How conformational changes can affect catalysis, inhibition and drug resistance of enzymes with induced-fit binding mechanism such as the HIV-1 protease

► We present a general model for enzymes with induced-fit binding mechanism. ► The enzymes change from an open to a closed conformation during binding. ► Non-active-site mutations affect catalysis and inhibition in the model. ► Mutations destabilizing the closed conformation contribute to multi-drug resistance. ► The mutation L90M of the HIV-1 protease slightly destabilizes the closed conformation.