Theoretical Studies Of Halogen And Hydrogen Bond Interactions In Biomolecular Systems

This work mainly focuses on two aspects.The first one is about the analysis about the inter-molecular interaction of hydrogen and halogen bond.A thorough investigation on the characteristics and mechanism of hydeogen and halogen bonding is of great significance for designing new functional materials,designing and synthesizing new drugs and carrying on supermolecular self-assembly.The second one is the concept of charge transfer network among amino acids,which provides alternative topological view of electronic properties for arbitrary proteins complexes.It could help us understand the topological features of the electronic structure for biological processes,Such as photosynthesis,respiration,and signal transduction of biology,enzymatic reactions,gene replication and mutation and so on.Our conclusions are summarized as follows1.The theoretical analysis of the FX dimer potential energy surface(PES)shows that the PES of intermolecular weak interaction for halogen...halogen(X...X)bond interaction exhibits significant anisotropic feature.We found that most DFT functionals give remarkably unphysical angular distortion of the PES.This is unlikely to be solved unless the functionals contain components that ensure the correct angular dependent behavior in the halogen bonding region.Threrfore,we suggested a simple empirical correction may substantially quantify this unphysical angular distortion,and further investigation is recommended.These findings constitute a step forward toward the understanding of the nature of X...X bonds and establish clear guidelines for the future designing of the state-of-art theoretical methods.2.The dynamical effects of hydrogen bonds play important roles in photoprotection mechanism of plant phenolic sunscreens.The sinapic acid(SA)derivatives play a critical role in preventing overexposure of UV-B to the underlying mesophyll layer where photosynthesis occurs.And we studied the impact of hydrogen bond dynamics in the excited state energy relaxation in the photoprotection mechanism of sinapic acid.Using a combination of ultrafast excited state dynamic simulations,together with classical molecular dynamics studies,we demonstrate that there is direct coupling of hydrogen bond motions with excited state energy relaxtion as part of the basic mechanism in solution.Beyond the intra-molecular degree of freedom,the inter-molecular motions are potentially important for the photoprotection mechanism events.These provide not only an enhanced understanding of the molecular mechanism of plant photoprotection,but also further insight for the future development of sunscreen agents.3.We proposed to use the clustering algorithm to analyze excited state dynamic trajectory in the big data scenario.As the excited states of polyatomic systems are rather complex,and often exhibit meta-stable dynamical behaviors.Static analysis of reaction pathway often fails to sufficiently characterize excited state motions due to their highly non-equilibrium nature.Here,we proposed a method to analyze the excited state dynamics of sunscreen using clustering algorithm.Based on the knowledge of these meta-stable patterns,we suggested the prediction with ensemble models(PEM)to accurately predict the ground and excited state properties of the entire dynamics trajectories.The PEM method does not require any training data beyond the clustering algorithm,and the estimation error for both ground and excited state is very close.Recently the PEM model have been used to improve the traditional molecular force field.4.The charge transfer network is constructed on the basis of the protein fragment interactions.And the data driven network(D2Net)model is also proposed to predict the electronic properties for arbitrary proteins complexes.Due to the highly complex chemical structure of biomolecules,the extensive understanding of the electronic information for proteomics can be challenging.We construct a charge transfer database at residue level derived from millions of electronic structure calculations among 20×20 possible amino acid side-chains combinations,which are extracted from available high-quality structures(<2.0 (?))of more than 2000 of protein complexes than contain all of these possible interactions of protein side-chain pairs.Then,the data driven network(D2Net)analysis can be applied to quickly identify the critical residue or residue groups for any possible protein structure.This work provides us a promising tool for efficiently understand electron information in the growing number of high-quality experimental protein complexes.