Nucleic oligonucleotide

DNA polymerase enzymes all synthesize DNA by adding deoxynucleotides to the free 3 -OH group of an RNA or DNA primer sequence. The identity of the inserted nucleotide is deterrnined by its abiHty to base-pair with the template nucleic acid. The dependence of synthesis on a primer oligonucleotide means that synthesis of DNA proceeds only in a 5%o V direction if only one primer is available, all newly synthesized DNA sequences begin at the same point. 

In Section II we provide an overview of the current status of nucleic acid simulations, including studies on small oligonucleotides, DNA, RNA, and their complexes with proteins. This is followed a presentation of computational methods that are currently being applied for the study of nucleic acids. The final section of the chapter includes a number of practical considerations that may be useful in preparing, performing, and analyzing MD simulation based studies of nucleic acids. 

Essential for MD simulations of nucleic acids is a proper representation of the solvent environment. This typically requires the use of an explicit solvent representation that includes counterions. Examples exist of DNA simulations performed in the absence of counterions [24], but these are rare. In most cases neutralizing salt concentrations, in which only the number of counterions required to create an electrically neutral system are included, are used. In other cases excess salt is used, and both counterions and co-ions are included [30]. Though this approach should allow for systematic smdies of the influence of salt concentration on the properties of oligonucleotides, calculations have indicated that the time required for ion distributions around DNA to properly converge are on the order of 5 ns or more [31]. This requires that preparation of nucleic acid MD simulation systems include careful consideration of both solvent placement and the addition of ions. 

Preorganization of DNA and improving nucleic acid recognition by synthetic oligonucleotides 97CRV1473. 

Wahlestedt C, Salmi P, Good L, Kela J, Johnsson T, Hokfelt T, Broberger C, Porreca F, Lai J, Ren K, Ossipov M, Koshkin A, Jakobsen N, Skouv J, Oerum H, Jacobsen MH, Wengel J (2000) Potent and nontoxic antisense oligonucleotides containing locked nucleic acids, Proc Natl Acad Sd USA 97 5633-5638... 

Nielsen P.E., Egholm M., Berg R. H., Buchardt O. Peptide nucleic acids (PNA) oligonucleotide analogs with a polyamide backbone. In Antisense Research and Applications. Crooke S.T., Le-BLBu B. (Eds). CRC Press, Boca Raton,... 

O. G. PNA-related oligonucleotide mimics and their evaluation for nucleic acid hybridization studies and analysis. Nucleosides, Nucleotides Nucleic Acids 2001 20 419-428. 

Boulm F., Freund F., Moreau S., Nielsen P.E., Gryaznov S., Toulme J.J., Litvak S. Modified (PNA, 2-O-methyl and phosphoramidate) anti-TAR anti-sense oligonucleotides as strong and specific inhibitors of in vitro HI.V.-l reverse transcription. Nucleic Acids Res. 1998 26 5492-5500. 

Sazani P., Kang S.H., Maier M.A., Wei C., Dillman j., Summerton J., Mano-haran M., Kole R. Nuclear antisense ef fects of neutral, anionic and cationic oligonucleotide analogs. Nucleic Acids Res. 2001 29 3965-3974. 

---