Linked Life Data

17705162

Source:http://linkedlifedata.com/resource/pubmed/id/17705162

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-6
pubmed:abstractText
Azole-bridged diplatinum compounds are promising new anticancer drugs designed to induce small distortions upon DNA alkylation, able to circumvent resistance problems of existing platinum drugs. Hybrid quantum classical (QM/MM) molecular dynamics (MD) simulations of different azole-bridged platinum drugs have recently revealed the nature of the local deformations at the DNA binding site. However, the description of global slow converging rearrangements cannot be addressed by QM/MM MD due to the short time scale accessible. Extensive classical MD simulations are therefore mandatory to describe accurately the structural distortions in the DNA double helix. This issue is now addressed by developing a new set of accurate force field parameters of the platinated moiety via a recently proposed force matching procedure of the classical forces to ab initio forces obtained from QM/MM trajectories. The accuracy of our force field parameters is validated by comparison of structural properties from classical MD and hybrid QM/MM simulations. The structural characteristics of the Pt-lesion are well reproduced during classical MD compared with QM/MM simulations and available experimental data. The global distortions in the DNA duplex upon binding of dinuclear Pt-compounds are very small and rather opposite to those induced by cisplatin. Thus, the force match approach significantly extends the potentialities of molecular simulations in the study of anticancer drugs and of the interactions with their biological targets.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0192-8651
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38-49
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Parameterization of azole-bridged dinuclear platinum anticancer drugs via a QM/MM force matching procedure.
pubmed:affiliation
Center for Molecular Modeling and Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA. katrin.spiegel@gmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't