Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. I. Research design and results on d(CpG) steps.
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 approximately 0.6 mus of simulation for systems containing approximately 24,000 atoms. The resulting trajectories involve 600,000 coordinate sets and represent approximately 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.
Beveridge
David L
DL
Chemistry Department, Molecular Biology & Biochemistry Department, and Molecular Biophysics Program, Wesleyan University, Middletown, Connecticut 06459, USA. dbeveridge@weselyan.edu
Barreiro
Gabriela
G
Byun
K Suzie
KS
Case
David A
DA
Cheatham
Thomas E
TE
Dixit
Surjit B
SB
Giudice
Emmanuel
E
Lankas
Filip
F
Lavery
Richard
R
Maddocks
John H
JH
Osman
Roman
R
Seibert
Eleanore
E
Sklenar
Heinz
H
Stoll
Gautier
G
Thayer
Kelly M
KM
Varnai
Péter
P
Young
Matthew A
MA
D001483:Base Sequence; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013329:Structure-Activity Relationship
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D004247:DNA