Computer Simulation For Inhibitor-enzyme Interaction And Recognition

Molecular recognition is of central importance in biology and pharmacology. It underlies the action ofhormones, the control of DNA transcription, the recognition of Antigens-Antibody in the immune system,the catalysis of chemical reactions by enzymes and the actions of many drugs. Calculations of absolutebinding free energy play a very important role in the study of the mechanism and dynamics of themolecular recognition. The orientation of chemical reactions depends on the sign of binding free energyand the tendency depending on its corresponding value. Many groups have invested ingenuity and effort inthe development of such models.Recently, much attention has been paid to studying of interactions and recognition ofbio-molecules by computer simulation approach. Molecule docking is one of the importantsimulation approaches and has many applications. The so-called molecule docking is toexamines whether the two molecules can bind and predict the binding mode based on thethree-dimensional structures of molecules. From the view of thermodynamics, native complexis the structure with the lowest binding free energy. Therefore, the aim of docking is to findthe conformation with the lowest binding free energy. There are important content in thispaper:1}Primary sequence of SARS E protein wa s aligned by bioinformatics methods. Thepossible 3-D structure of E protein were constructed using Insight II/ biopolymer module,molecular dynamics methods was adapted to obtained the most stabilized conformation atliberty, the reliability of SARS E proteins model is evaluated with Profile-3D. Active site andkey residue were predicted according to conserved region and variable region of sequence.Memberan protein E was embedded POPC. The simulation result is helpful of providinginsights into understanding the functions of SARS E proteins and to establish molecularmodels and target for screening anti-SARS drug design.2} We have examined the anti-(SARS 3CLpro) activity of five polyoxometalates. DFTcalculations have been first carried out on five [α-PTi2W10O40]7- isomers to investigateelectronic properties, redox properties, protonation, and stability. The high negative chargeand the general dimensions of this unique structure led us to examine the inhibitory potentialof these compound against SARS 3CLpro.The results of the kinetic analysis suggest that thesepolyoxometalates inhibit 3CLpro by binding specifically to the active site, thereby precluding.That hydrolyze the two polypeptides expressed by the virus, thus cut off the approach of virusreplication.