Insights into (S)-rivastigmine inhibition of butyrylcholinesterase (BuChE): Molecular docking and saturation transfer difference NMR (STD-NMR)

Rivastigmine is a very important drug prescribed for the treatment of Alzheimer's disease (AD) symptoms. It is a dual inhibitor, in that it inhibits both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). For our screening program on the discovery of new rivastigmine analogue hits for human butyrylcholinesterase (hBuChE) inhibition, we investigated the interaction of this inhibitor with BuChE using the complimentary approach of the biophysical method, saturation transfer difference (STD)-NMR and molecular docking. This allowed us to obtain essential information on the key binding interactions between the inhibitor and the enzyme to be used for screening of hit compounds. The main conclusions obtained from this integrated study was that the most dominant interactions were (a) H-bonding between the carbamate carbonyl of the inhibitor and the NH group of the imidazole unit of H434, (b) stacking of the aromatic unit of the inhibitor and the W82 aromatic unit in the choline binding pocket via pi-pi interactions and (c) possible CH/pi interactions between the benzylic methyl group and the N-methyl groups of the inhibitor and W82 of the enzyme.

Modelling and PI Control of an Irrigation Canal

The main goal of this paper is to expose and validate a methodology to design efficient automatic controllers for irrigation canals, based on the Saint-Venant model. This model-based methodology enables to design controllers at the design stage (when the canal is not already built). The methodology is applied on an experimental canal located in Portugal. First the full nonlinear PDE model is calibrated, using a single steady-state experiment. The model is then linearized around a functioning point, in order to design linear PI controllers. Two classical control strategies are tested (local upstream control and distant downstream control) and compared on the canal. The experimental results show the effectiveness of the model.