Development And Applications Of Theoretical Method For Complex Systems

With the development of computer technology,the methods of theoretical calculations are applied to the chemical,biological,physical,material and other fields is becoming more common,the applications vary from the validation of experimental results to guide the proceedings of experiment.Developing both inexpensive and high accurate theoretical methods is becoming more and more urgent.The density functional theory?DFT?method is cheaper than other high-precision quantum chemistry methods,and is more accurate than molecular mechanics methods,which is in line with the development trend of current theoretical methods.In the past 30 years,Kohn-Sham Density Functional Theory?KS-DFT?has become the most effective and popular electronic structure method in chemical and condensed matter physics.Applications of KS-DFT involve large or complex molecules,metals,catalysis,kinetics and nanotechnology.However,the accuracy of KS-DFT depends on the quality of the exchange-correlation functionals,and the exact form of the functional is unknown.In order to gain a better approximation of the absolute exchange-correlation functional,the researchers have made great efforts.Useful functionals should be high accuracy and less calculation,because high cost performance is the main driver for the widespread use of KS-DFT.The M06 series of functionals developed by the Minnesota University can be widely applied to a variety of physical and chemical properties,including M06-L as the local density functional,M06 and M06-2X as the hybrid density functional.In this paper,in order to achieve a higher overall accuracy and improvements of the chemical reaction barrier heights,noncovalent interaction,and the accuracy of the lattice constant,by fitting to a larger database?including molecular and solid crystal data?than the original M06-L functional,the revM06-L is developed.The revM06-L functional gives both smoother potential energy curves and improved overall accuracy,especially for chemical reaction barrier heights,noncovalent interactions,and solid-state physics.Recently,Medvedev and co-workers have suggested that some of the recently developed density functional theory methods would yield more accurate energy at the expense of the accuracy of the electron density.In this work,two basic sets are used,namely,aug-cc-p?CV5Z and aug-cc-pV5Z.The electron densities of Ne,Ne⁶⁺and Ne⁸⁺are calculated by 17 different density functionals,Hartree-Fock and MP2 methods.We found that the choice of basis set has a significant impact on the errors and rankings of some of the selected methods.The errors of electron densities,their gradients,and Laplacians calculated with the aug-cc-pV5Z basis set are substantially reduced,especially for Minnesota density functionals,as compared to the results using the aug-cc-p?CV5Z basis set.The rankings of the M06 suite of functionals among the 19methods are greatly improved with the aug-ccpV5Z basis set.The M06 suite of functionals is capable of providing accurate electron densities,gradients,and Laplacians using the aug-cc-pV5Z basis set,and thus it is suitable for a wide range of applications in chemistry and physics.Finally,we combined quantum mechanics methods with molecular mechanics methods,such as molecular docking,molecular dynamics simulation and protein-ligand interaction energy calculation?MM/PBSA?.The multi-level calculation methods are applied to complex biological systems such as protein-ligand complex.Specifically,we use a variety of calculation methods to find the possible strong binder of the acute coronary syndrome drug target,protein PAR1,from two molecule databases.The two databases are Specs database including more than 200000 small molecules and 3000molecules in traditional Chinese medicine?TCM?database.Combining molecular docking method,molecular dynamics simulation and the protein-ligand binding free energy calculations with MM/PBSA method and density functional method,we found14 possible small molecules can strongly bind with PAR1.Furthermore,aflatoxin B1is a highly toxic carcinogen that can be produced from a variety of moldy foods and is crucial in food safety testing.We searched for the possible affinity protein of aflatoxin B1 through a variety of computational methods.Three proteins,trihydroxy naphthalene reductase,GSK-3b and Pim-1,were selected as aflatoxin affinity protein.GSK-3b and Pim-1 are drug targets for cancer and neurological diseases.GSK-3b is the strongest binder to aflatoxin B1.