Development And Application Of Quantum Chemistry Fragmentation Method For Large Biomolecules In Excited-State

RNA fluorescence imaging technology can provide new methods for the treatment of related diseases.The absorption of light by rhodopsin is a new photosynthetic pathway different from that of green plants.The further study of bioluminescence system cannot be done without the help of the prediction of quantum chemistry theory.However,the exponential increase in the calculation amount caused by thousands of atoms in biological system makes people afraid of it,so the quantum chemical fragmentation method emerged.Electrostatically Embedded Generalized Molecular Fractionation with Conjugate Caps(EE-GMFCC)method is a linear scaling quantum chemistry method.In this paper,the Ground-State EE-GMFCC method is summarized,and the EE-GMFCC method is developed and applied to the Excited State system.The First Chapter introduces the theoretical and computational chemistry knowledge necessary for the EE-GMFCC method research.Including quantum chemical calculation theory,molecular dynamics simulation,molecular excited state calculation method,quantum mechanical fragmentation method,RNA aptamer fluorescence system,rhodopsine,etc.The first chapter also introduces the structure and innovation of this paper.Chapter 2 introduces the Ground-State EE-GMFCC method.(1)It summarizes and gives the process of Ground-State energy by EE-GMFCC,explains in detail the two double-counting calculation methods in the EE-GMFCC,and uses FORTRAN programming language to achieve.(2)The Ground-State EE-GMFCC method was applied to protein system and RNA system,and the results show that the Ground-State EE-GMFCC method has good accuracy.Although the two double-counting calculation ways are different,while the two results are the same.(3)We also explore the effection on ?(the cutoff of two-body)to the result of ground-state EE-GMFCC method in protein system.After balancing the accuracy and calculation time we hold the opinion that the optimal value of ? was 4 ?.In Chapter 3,the Ground-State EE-GMFCC method was extended to the ExcitedState system.(1)The performance of the EE-GMFCC on prediction of the absolute excitation energies,the corresponding transition electric dipole moment(TEDM),and atomic forces at both the TD-HF/6-31G* and TD-DFT/6-31G* levels were tested using the Mango-II RNA aptamer system as a model system.The results demonstrate that the calculated Excited-State properties by EE-GMFCC are in excellent agreement with the traditional full system QM calculations.EE-GMFCC method is linear-scaling with a low prefactor.(2)The fragmentation method further provides a straightforward approach to decompose the excitation energy contribution per ribonucleotide around the fluorophore and then reveals the influence of the local chemical environment on the fluorophore.(3)Moreover,the EE-GMFCC method is capable of providing an accurate prediction of the relative conformational excited-state energies for different configurations of the Mango-II RNA aptamer system extracted from the Molecular Dynamics(MD)simulations.(4)The applications of EE-GMFCC in calculations of excitation energies for other RNA–fluorophore complexes demonstrate that the EEGMFCC method is a general approach for accurate and efficient calculations of Excited-State properties of fluorescent RNAs.In Chapter 4,the Excited-State EE-GMFCC method is applied to calculate the excitation energy of protein system.(1)Excitation energies of 10 variants of Blue Proteorhodopsin(BPR-PR105Q)in residue 105 GLN were calculated with the EEGMFCC method at the TD-B3LYP/6-31G* level.The calculated results show good correlation with the experimental values of absorption wavelengths,although the experimental wavelength range among these systems is less than 50 nm.This demonstrates that the EE-GMFCC method could be applied to accurately predict the absorption spectral shifts for biomacromolecules.(2)The distance between residues and the chromophore were given by introducing three kinds of formulas of distance between polyatomic system.The position and side-chain direction of residues were analyzed from the function between residues' distance and its sequence number.(3)The excitation wavelength distributions of 100 conformations of each mutation of PR105 Q calculated by the Excited-State EE-GMFCC method are normal distribution,and its average value is close to the experimental value.(4)The ensemble-averaged electric fields along the polyene chain of retinal correlated well with EE-GMFCC calculated excitation energies for these 10 PRs,suggesting that electrostatic interactions from nearby residues are responsible for the color tuning.(5)We also utilized the GMFCC method to decompose the excitation energy contribution per residue surrounding the chromophore.Our results show that residues ASP97 and ASP227 have the largest contribution to the absorption spectral shift of PR among the nearby residues of retinal.The Chapter 5 summarizes and anticipates the whole paper.In summary,this paper mainly has the following three innovations: 1.The GroundState EE-GMFCC method is sorted out and applied,and the calculation process of two double-counting in EE-GMFCC are explained in detail.2.The Ground-State EEGMFCC method was extended to the Excited-State and applied to RNA-fluorescent aptamer system.3.The excited state EE-GMFCC method was applied to calculate the excitation energy of Proteo Rhodopsin(PR)and its mutants.