This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Peptide nucleic acids (PNA) are synthetic analogs of DNA which contain the samenucleobases as those in DNA but in which the sugar phosphate is replaced by astructurally homomorphous pseudopeptide chain. PNA forms by Watson Crickbasepairing duplexes that are homomorphous to DNA ones. PNA strands can bindto other PNA strands%2C to DNA and to RNA. The computer time requested in thisapplication will be used to investigate metal-containing alternative base pairsthat can be introduced in PNA. The pursuit of these alternative basepairs hasbiological relevance because it will provide information relevant to assess thepotential of these basepairs to store information by using coordinative bondsinstead of hydrogen bonds%2C in a manner similar to that of the genetic code.In addition, the new hybrid PNA-metal molecules have properties that can beused in molecular electronics applications. Major thrusts in molecularelectronics are the discovery of new molecules with nanometer dimensions thatcan function as molecular wires or devices and of methods for assembly of thesemolecules in nanosize circuits.We have discovered that peptide nucleic acid (PNA)%2C a synthetic analog ofDNA%2C can be used as scaffold for metal ions by substitution of nucleobaseswithin PNA oligomers with ligands that confer high affinity for metal ions tothe PNA duplexes. As a consequence, the modified duplexes are bridged by acombination of hydrogen and coordinative bonds. We use this strategy for thecontrolled assembly of nanostructures containing TM ions based onligand-modified PNA helical duplexes.Our approach offers control over the type and position of metal ionsincorporated in the duplexes and enables us to place TM ions at specificlocations in 1-D structures and to create metal arrays of sizable length.The specific goal of this proposal is to use molecular dynamics simulations toexplore the structure of metal-containing PNA duplexes. Recent moleculardynamics studies of PNA-PNA and PNA-DNA duplexes show that PNA strands maintainstable double helical structures. Simulations started with either A-DNA orB-DNA converged to PNA structures that were in good agreement with reported NMRand crystallographic observations.Initial coordinates for the nucleic acid scaffold will be obtained from a B-DNAcanonical double-helix with the same sequence as P. The sugar-phosphatebackbone will be replaced with the peptide backbone%2C according to thecorrespondence between the PNA and DNA atoms. The molecular dynamics software that we plan to use is AMBER. The force fieldparm94 will be complemented with previously determined parameters for the PNAbackbone. Coordinates and charges for %5BPt(bypiridine)2%5D2%2B have alreadybeen obtained by students in our lab using Gaussian98 with the B3LYP hybridfunctional and the standard LANL2DZ basis set. Charges for PNA atoms were alsoalready obtained using an HF%2F6-31G%2A basis set.We are requesting a starting grant of 30%2C000 service units on ben to initiatethe simulations and obtain benchmarks.
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