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In the QM/MM simulations the two subsystems are electrostatically and mechanically coupled as described in ref.[22] The quantum system was terminated at the QM/MM boundary with hydrogen atoms saturating the valence of the boundary atoms. Since these added hydrogen atoms must interact with the quantum but not with the classical sub-system, their electrostatic interaction with the nearby classical atoms was shielded in order to avoid the formation of unphysical hydrogen bonds with the nearby classical atoms To that end, the MM atoms covalently connected to QM atoms are coupled with the quantum system by a Coulomb potential with a set of ESP-like charges, localized on the QM atoms and defined as described in ref [51] In this manner, pair interactions that have to be shielded can be explicitly excluded from the interaction Hamiltonian
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5444270257
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The functional of choice for most calculations was the BLYP functional.[52 53] Since it was suggested that other "pure" functionals (e g HCTH[54 55]) give better results than BLYP for deprotonation and transition state energies,[55] in a few cases we repeated the calculations with that functional, but the energy differences that we obtained for our system were well within the error bar.[55] The Kohn-Sham orbitals were expanded up to an energy cutoff of 70 Ry and the calculations were made in the local spin density framework (i e, singly occupied orbitals) The classical region that included all the remaining atoms was treated with the Amber force field[56]
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5444239990
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Assuming τ ≈ 1
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46
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5444259588
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note
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In reducing conditions this precursor is converted into 2,6-diamino-4-hydroxy-5-formamidopyrimidine nucleoside (FapyG).[1]
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47
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5444233327
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Calculations on this alternative oxidation pathway are in progress and preliminary results indicate the existence in DNA of a barrier to oxygen attack due to steric hindrance posed by neighboring bases
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Starting from 300 K the temperature was cooled down to 2 K, rescaling the velocities by a factor of 0 99 each step. This procedure, while ensuring convergence to a local minimum, generally does not allow for major rearrangements of the structure. However in this case we started from a geometry that was already optimized and whose close packing of the atoms taken from the X-ray crystal structure[34] does not allow much rearrangement of the backbone
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