Study Of Structure-Activity Relationship By Multiscale Theoretical Chemistry

There are many difficult problems in the theoretical study of chemical physics.From the macroscopic level of macromolecule to the microscopic level of electronic properties,the structure-activity relationship has been the focus of our attention.At present,the commonly used theoretical calculation simulation methods are mainly quantum chemistry calculation and molecular dynamics simulation.This paper analyzes and studies the key role of structural change on properties and mechanism by establishing multi-scale models for two popular systems.In the aspect of life science,the different conformations of ATP-binding cassette transporters(ABC proteins)and their effects on transport mechanism were studied by molecular dynamics simulation.In the aspect of materials science,the relationship between the structures and activities of electrocatalysts was analyzed by quantum chemistry calculation.Firstly,molecular dynamics simulations of ABC proteins were performed by means of all-atomic modeling combined with coarse-grained modeling.ATP-Binding Cassette(ABC)transporters use energy from ATP binding and hydrolysis to actively transport a wide variety of substrates across the lipid membrane by alternating between inward-facing(IF)and outward-facing(OF)states of the transmembrane domains(TMDs).However,the structural determinants of the conformational change and their functional roles are not fully understood.In our work,the crystal structure of ATPbinding cassette transporter(Sav1866)in S.aureus was used for coarse-grained molecular dynamics simulation combined with going backward to all-atom model structural analysis.A reliable pathway is determined by comparing the X-ray experimental results with the stable structures obtained by the calculation of the potential of mean force(PMF).The results of the simulation show that the transmembrane domains have obvious cooperative effect in the process of conformational changes with the dimerization and dissociation of the nucleotide binding domains(NBDs).The structural and dynamical analyses identify the structural determinants and their functional roles in the structural transition,meanwhile they reveal the characteristics of unidirectional transport in ABC proteins and we proposed a "conformational selection" transport mechanism.After this,coarse-grained and allatomic molecular modeling was used for MsbA-mediated Lipopolysaccharide(LPS)transport observed by cryo-electron microscopy in Gram-negative bacteria.The process and the structures of conformational changes of MsbA in the presence or absence of the transport substrate lipopolysaccharide were compared and analyzed.The simulation results indicated that the specificity of transport substrates have an important impact on the overall transport process,and also verified the previously proposed the transport mechanism of "conformational selection".Then,density functional theory(DFT)calculations were used to study the effects of different sturctures on the electrocatalytic activities in Pd1-NxCy single atom catalysts(SACs).The development of highly active SACs for electrochemical reactions is the key to future renewable energy technologies.A large number of experiments and theoretical studies have shown that nitrogen-doped graphene based SACs have good application prospects in electrochemical reactions,but the influence of the local coordination environment of the single metal atom on the electrochemical activity is still not well understood yet.Herein,effects of the local coordination numbers and coordinated components of a single Pd atom in Pd1-NxCy on the hydrogen evolution reaction(HER)and oxygen reduction reaction(ORR)activities were systematically investigated using theoretical calculations.We found that change in the local coordination environment is an effective way to modulate the electrochemical activities,the four-atom-coordinated Pd1-N2C2-2 and the three-atom-coordinated Pd1-N3C0-3 were the most promising HER and ORR electrocatalysts,respectively.This work provides valuable insights into designing more efficient electrocatalysts for HER and ORR,as well as the other important electrochemical processes.