| DNA molecules and metalloenzymes play an important role in the life domain.Inrecent years,the multidisciplinary research on DNA and enzyme has attractedconsiderable attention and remarkable progresses have been made.However,at theatomic scale level,understanding of these unique biological systems in biology andtheir molecular mechanisms involved in the bio-related chemical processes is stilldifficult and challenging.Here selected biological systems relative to DNA andmetalloenzymes were considered and their structural features and chemicalreactivities were investigated theoretically.On the basis of extensive calculations,wetry to understand fundamental aspects of DNA damages from the low energy electronattachment and catalytic mechanisms of metalloenzymes.The main results in this dissertation are summarized as follows:(1)Our calculations show that the dehydrogenation at the N9 site in the adenine andguanine transient anions is the lowest-energy channel to loss of hydrogen.For theadenine anion,as the N9-H bond stretches,the low-energy electron configurationmay change from the initialπ* state to theσ* state,and theπ*-σ* energy curvesintersect at 1.22(?).While the guanine anion has a character of dipole-bound state,and its fragmentation is not sensitive to the low energy electron attachment.(2)For the Watson-Crick adenine-thymine(A-T)base pair,the electron attachment tothe A-T base pair and its derivatives significantly modifies the hydrogen bondinteractions and results in remarkable structural changes.The relatively low-costhydrogen eliminations correspond to the cleavage of(N9)-H(adenine)and(N1)-H(thymine)bonds.In the dehydrogenating process,the anionic A-T fragmentgradually changes its electronic configuration fromπ* toσ* state,like the singlebases adenine and thymine.(3)The low-energy electron attachment to the pyrimidine nucleotides mayremarkably modify their equilibrium geometries,electron affinities,and bonddissociations.The C5′-O5′and C1′-N1 bonds of the anionic dCMP and dTMP were predicted to be relatively easy to break relative to their neutral species.The C-Obond cleavage has relatively low activation energy with respect to C-N bondbreaking,and the presence of the solvent water may significantly reduce theactivation energy in the C-N bond cleavage process.Present results provide abasis for understanding the single strand breaks in DNA induced by low-energyelectron attachment.(4)Density functional theory and combined quantum mechanics and molecularmechanics(QM/MM)calculations have been used to explore structural features ofthe FeMo cofactor with an interstitial atom X(X = N,C,or O)and its interactionswith CO and N2.Predicted frequencies of the metal-bound CO,QM/MM-optimized geometries,and calculated redox potentials of the FeMocofactor with different central ligands show that the oxygen atom is the candidatefor the interstitial atom.Calculations on the interactions of the FeMo cofactor withCO and N2 reveal that there is a remarkable dependence of the binding energy onthe binding site and the interstitial atom.Generally,the Fe2 site of the FeMocofactor has stronger interactions with CO and N2 than Fe6,and both the Fe2 andFe6 sites in the N-centered and O-centered clusters of the FeMo cofactor caneffectively bind N2 while the coordination of N2 to the Fe6 site of the C-centeredactive cluster is unfavorable energetically.Present results indicate that the proteinenvironment is important for computational characterization of the structure of theFeMo cofactor and properties of the metal-bound CO and N2 are sensitive to theinterstitial atom.(5)The catalytic oxidation of CO to CO2 by carbon monoxide dehydrogenases hasbeen explored theoretically,and a large C-cluster model including the metal core[Ni-4Fe-4S]and surrounding residues and crystal water molecules was used indensity functional calculations.On the basis of computational results,theplausible enzymatic mechanism for the CO oxidation was proposed.In thecatalytic reaction,the first proton abstraction from the Fel-bound water leads to aprecursor to accommodate CO binding and the subsequently consecutive proton transfer from the metal-bound carboxylate to the amino acid residues facilitatesthe release of CO2.The hydrogen-bond network around the C-cluster,formed byconserved residues His93,His96,Glu299,Lys563,and four water molecules inthe active domain plays an important role in the proton transfer and theintermediate stabilization.Predicted geometries of key species show goodagreement with their reported crystal structures.(6)The oxidative half-reaction of oxygen atom transfer from nitrate to MoⅣcomplexwas investigated theoretically.Calculations show that the nitrate reduction canoccur through either a direct rupture of Mo-ONO2-bond or a bond formationbetween the nitrate ion and a Mo-bound sulfur ligand.Detailed mechanisms andreaction energetics were predicted.Present results indicate that the formation of adisulfide bond can mediate the oxidation-state interconversion of the metal centerfrom MoⅥto MoⅣ,which plays an important role in the nitrate reduction reaction. |
