title: Factors determining the deriving force of DNA formation: geometrical differences of base pairs, dehydration of bases, and the arginine assisting.
abstract: The mechanism of the fidelity synthesis of DNA associated with the process of dGTP combination to the DNA template was explored. The exclusion of water molecules from the hydrated DNA bases can amplify the energy difference between the correct and incorrect base pairs, but the effect of the water molecules on the Gibbs free energy of formation is dependent on the binding sites for the water molecules. The water detachment from the incoming dNTP is not the only factor but the first step for the successful replication of DNA. The second step is the selection of the DNA polymerase on the DNA base pair through the comparison between the correct DNA base and the incorrect DNA base. The bonding of the Arg668 with the incoming dNTP can enlarge the Gibbs free energies of formation of the base pairs, especially the correct base pairs, thus increasing the driving force of DNA formation. When the DNA base of the primer terminus is correct, the extension of the guanine and the adenine is quicker than that of the cytosine and the thymine because of the hydrogen bonding fork formation of Arg668 with the minor groove of the primer terminus and the ring oxygen of the deoxyribose moiety of the incoming dNTP. Because of the geometry differences of the incorrect base pairs with the correct base pairs, the effect from the DNA polymerase is smaller on the incorrect base pair than on the correct base pair, and the extension of a mispair is slower than that of a correct base pair. This decreases the extension rate of the base pair and thus allows proofreading exonuclease activity to excise the incorrect base pair. Arg668 cannot prevent the extension of the GT mispair, as well as the GC correct base pair, and GA and GG mispairs. This may be attributed to the small geometry difference between the GT base pair and the correct AT base pair.
authors.affiliation: Institute of Theoretical Chemistry, Shandong University, Jinan, 250100, P. R. China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Sun
authors.forename: Robert I
authors.initials: RI
authors.lastname: Cukier
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Bu
mesh_terms: D000225:Adenine / Q000737:chemistry; D001120:Arginine / Q000737:chemistry*; D020137:Base Pair Mismatch; D020029:Base Pairing; D001665:Binding Sites; D003596:Cytosine / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D003681:Dehydration; D003848:Deoxyguanine Nucleotides / Q000737:chemistry; D003855:Deoxyribose / Q000737:chemistry; D006147:Guanine / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism; D013698:Templates, Genetic; D013941:Thymine / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D003848:Deoxyguanine Nucleotides; D014867:Water; D003855:Deoxyribose; D006147:Guanine; C029603:deoxyguanosine triphosphate; D003596:Cytosine; D004247:DNA; D001120:Arginine; D012194:RNA-Directed DNA Polymerase; D000225:Adenine; D013941:Thymine; D010100:Oxygen