Study Of The Theoretical Calculations Of The Interaction Between Protein MDM2 And Inhibitor IMZ

Quantum dynamics study of polyatomic reaction and accurate quantum mechanical calculation for biological molecules such as proteins are very important topics in computational chemistry and biology. Over the past twenty years, with the development of quantum scatting theory and the enhancement of computational capacity, it has been possible to take full quantum calculation on reactions with no more than four atoms. But in chemical and biological fields, reactions always deal with more than four atoms. A grand challenge in computational chemistry and biology is the accurate quantum mechanical calculation of interaction energies for biological molecules such as proteins. Due to the larger number of atoms in proteins, the standard quantum chemistry could not be extended to protein systems.From the nineties of the last century, advance in computer science, medicine chemistry, molecular biology and computational chemistry have made protein simulation become a well-established and important research area. And protein simulation has become a powerful tool for biology experiments and drug design.During the past several decades, molecular dynamics (MD) simulation of proteins has become a widely used tool to deepen our understanding of molecules. Computer simulation techniques can be used to understand the properties of a molecular system in terms of interactions at the atomic level. The results of MD simulations are very useful to understand the relation between the macromolecular conformational changes and its biological function.In this paper, the absolute binding free energy of murine double mimute2 with a potent purine-base inhibitor IMZ was calculated by molecular dynamics simulations with MM-PBSA/GBSA methods, and reasonable results were obtained. Furthermore, the interaction between MDM2 and IMZ was evaluated by energy decomposition analysis. It is found that the result -32.41kcal/mol agrees well with experimental data. Calculations of absolute binding free energy play a very important role in the study of the mechanism and dynamics of the molecular recognition. The theoretical structures of the proteins will support the further studies on them, and our results can direct design of new inhibitors and drugs.Cancer is one of the most difficulty captured disease, which is considered as gene disease.P53 is a kind of inhibit protein. MDM2 is a oncoprotein that inhibits activity of P53 by binding to the domain of P53. The depressed ability of P53 aroses cancer. Here we report the interaction of between inhibitor IMZ(drug) and protein MDM2. The intention of interaction is to keep the action of P53 to inhibit cancer.At last, we not only provide the location, nature, strength of the drug-protein interaction, but also give the binding free energy values by two methods. These experiments can not be provided, it reveals the important residues that impact the ligand. And it provides the imformation and useful assistance for the further design of small molecule inhibitors, as well as drug workers in the molecular structure of the forecast, drug design and screening.