Quantum Chemical Study On The Interaction Between Beta-2 Adrenergic Receptor And Ligands

Mainly focused on the semi-empirical quantum chemistry theory, we studied on the interaction between beta-2 adrenergic receptor and different ligands, looking forward to develop more accurate molecular docking scoring function based on quantum mechanics theory. On one hand, available scoring functions based on empirical, knowledge or force field, couldn’t deal with the complex situations such as charge transfer and strong polarization, so it’s necessary to develop more accurate scoring function. On the other hand, with recent development and improvement of hardware performance, the semiempirical quantum chemistry methods such as PM7 make it possible to obtain the solution of quantum mechanics equation about large molecular systems such as protein efficiently, calculating the weak intermolecular interaction more accurately. Hence, adopting MOPAC2012 as the main sofware tool, we focused on PM7 model to theoretically calculate the interaction binding energy between beta-2 adrenergic receptor and multiple ligands, classifying different subtypes initially. We worked as follows:Firstly focused on semi-empirical quantum chemistry method PM7, we proposed effective scoring method to calculate interaction energy between beta-2 adrenergic receptor and multiple ligands, classifying different subtypes. We introduced the development of current scoring functions, interaction theory from molecular level, calculating methods about free binding energy and theoretical methods about enthalpy on PM7 model. On the basis of available beta-2 adrenergic receptor complex structures, we proposed quantum chemistry scoring method to calculate interaction energy between particular receptor and ligand. Then based on interaction characteristics between receptor and different subtypes, we obtained lots of complex conformations by molecular docking and then adopted PM7 scoring method to calculate binding energy between the receptor and ligand. After docking analyses, the results showed quantum chemistry calculation could find the best binding pose between the receptor and ligand, developing a molecular docking scoring method potentially.Then for three different subtypes, using quantum chemistry method with molecular dynamics simulation, we studied on the interaction between the receptor and ligands, achieving better improvement. Based on MM-PBSA theory and proposed calculating methods, we calculated interaction energy between beta-2 adrenergic receptor and ligands and contribution energy of important residues nearby binding pocket. By quantum chemistry method, we calculated binding energy based on different frame structures and the results showed there were some differences. These achievements could provide theoretical value and an important reference for the future research.