KAUST DepartmentPhysical Sciences and Engineering (PSE) Division
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AbstractHybrid QM/MM calculations on adducts of cisplatin with DNA dimer and octamer are reported. Starting from the crystal structure of a cisplatin-DNA dimer complex and an NMR structure of a cisplatin-DNA octamer complex, several variants of the ONIOM approach are tested, all employing BHandH for the QM part and AMBER for MM. We demonstrate that a generic set of molecular mechanics parameters for description of Pt-coordination can be used within the subtractive ONIOM scheme without loss of accuracy, such that dedicated parameters for new platinum complexes may not be required. Comparison of optimised structures obtained with different strategies indicates that electrostatic embedding is vital for proper description of the complex, while inclusion of water molecules as explicit solvent further improves performance. The resulting DNA structural parameters are in good general agreement with the experimental structure obtained, particularly when the inherent variability in NMR-derived parameters is taken into account. © 2012 Elsevier B.V.