QM/MM studies of cisplatin complexes with DNA dimer and octamer

Handle URI:
http://hdl.handle.net/10754/562260
Title:
QM/MM studies of cisplatin complexes with DNA dimer and octamer
Authors:
Gkionis, Konstantinos; Platts, James A.
Abstract:
Hybrid 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.
KAUST Department:
Physical Sciences and Engineering (PSE) Division
Publisher:
Elsevier BV
Journal:
Computational and Theoretical Chemistry
Issue Date:
Aug-2012
DOI:
10.1016/j.comptc.2012.05.034
Type:
Article
ISSN:
2210271X
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorGkionis, Konstantinosen
dc.contributor.authorPlatts, James A.en
dc.date.accessioned2015-08-03T09:58:25Zen
dc.date.available2015-08-03T09:58:25Zen
dc.date.issued2012-08en
dc.identifier.issn2210271Xen
dc.identifier.doi10.1016/j.comptc.2012.05.034en
dc.identifier.urihttp://hdl.handle.net/10754/562260en
dc.description.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.en
dc.publisherElsevier BVen
dc.subjectCisplatinen
dc.subjectDensity functional theoryen
dc.subjectDNAen
dc.subjectONIOMen
dc.subjectQM/MMen
dc.titleQM/MM studies of cisplatin complexes with DNA dimer and octameren
dc.typeArticleen
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.identifier.journalComputational and Theoretical Chemistryen
dc.contributor.institutionSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, United Kingdomen
kaust.authorGkionis, Konstantinosen
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