Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. I. Research design and results on d(CpG) steps

David L. Beveridge, Gabriela Barreiro, K. Suzie Byun, David A. Case, Thomas E. Cheatham, Surjit B. Dixit, Emmanuel Giudice, Filip Lankas, Richard Lavery, John H. Maddocks, Roman Osman, Eleanore Seibert, Heinz Sklenar, Gautier Stoll, Kelly M. Thayer, Péter Varnai, Matthew A. Young

Research output: Contribution to journalArticlepeer-review

236 Scopus citations

Abstract

We describe herein a computationally intensive project aimed at carrying out molecular dynamics (MD) simulations including water and counterions on B-DNA oligomers containing all 136 unique tetranucleotide base sequences. This initiative was undertaken by an international collaborative effort involving nine research groups, the "Ascona B-DNA Consortium" (ABC). Calculations were carried out on the 136 cases imbedded in 39 DNA oligomers with repeating tetranucleotide sequences, capped on both ends by GC pairs and each having a total length of 15 nucleotide pairs. All MD simulations were carried out using a well-defined protocol, the AMBER suite of programs, and the parm94 force field. Phase I of the ABC project involves a total of ∼-0.6 μs of simulation for systems containing ∞24,000 atoms. The resulting trajectories involve 600,000 coordinate sets and represent ∞400 gigabytes of data. In this article, the research design, details of the simulation protocol, informatics issues, and the organization of the results into a web-accessible database are described. Preliminary results from 15-ns MD trajectories are presented for the d(CpG) step in its 10 unique sequence contexts, and issues of stability and convergence, the extent of quasiergodic problems, and the possibility of long-lived conformational substates are discussed.

Original languageEnglish
Pages (from-to)3799-3813
Number of pages15
JournalBiophysical Journal
Volume87
Issue number6
DOIs
StatePublished - Dec 2004

Fingerprint

Dive into the research topics of 'Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. I. Research design and results on d(CpG) steps'. Together they form a unique fingerprint.

Cite this