μABC: A systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA

Marco Pasi, John H. Maddocks, David Beveridge, Thomas C. Bishop, David A. Case, Thomas Cheatham, Pablo D. Dans, B. Jayaram, Filip Lankas, Charles Laughton, Jonathan Mitchell, Roman Osman, Modesto Orozco, Alberto Pérez, Daiva Petkevičiute, Nada Spackova, Jiri Sponer, Krystyna Zakrzewska, Richard Lavery

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

We present the results of microsecond molecular dynamics simulations carried out by the ABC group of laboratories on a set of B-DNA oligomers containing the 136 distinct tetranucleotide base sequences. We demonstrate that the resulting trajectories have extensively sampled the conformational space accessible to B-DNA at room temperature. We confirm that base sequence effects depend strongly not only on the specific base pair step, but also on the specific base pairs that flank each step. Beyond sequence effects on average helical parameters and conformational fluctuations, we also identify tetranucleotide sequences that oscillate between several distinct conformational substates. By analyzing the conformation of the phosphodiester backbones, it is possible to understand for which sequences these substates will arise, and what impact they will have on specific helical parameters.

Original languageEnglish (US)
Pages (from-to)12272-12283
Number of pages12
JournalNucleic acids research
Volume42
Issue number19
DOIs
StatePublished - Oct 29 2014

All Science Journal Classification (ASJC) codes

  • Genetics

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