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.

Bases Moléculaires et Structurales des Systèmes Infectieux CNRS UMR 5086 Université Lyon 1 IBCP 7 Passage du Vercors 69367 Lyon France

BioMaPS Institute and Deptartment of Chemistry and Chemical Biology Rutgers University 610 Taylor Road Piscataway NJ 08854 8087 USA

Department of Chemistry Indian Institute of Technology Hauz Khas New Delhi 110016 India

Department of Chemistry Wesleyan University Middletown CT 06459 USA

Department of Medicinal Chemistry University of Utah Skaggs 307 Salt Lake City UT 84112 USA

Department of Structural and Chemical Biology Mount Sinai School of Medicine New York NY 10029 USA

Departments of Chemistry and Physics Louisiana Tech University Ruston LA 71270 USA

Institute of Biophysics Academy of Sciences of the Czech Republic Kralovopolska 135 612 65 Brno Czech Republic

Institute of Biophysics Academy of Sciences of the Czech Republic Kralovopolska 135 612 65 Brno Czech Republic CEITEC Central European Institute of Technology Masaryk University Campus Bohunice Kamenice 5 625 00 Brno Czech Republic

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Flemingovo nam 2 166 10 Praha 6 Czech Republic

Joint BSC CRG IRB Program on Computational Biology Institute of Research in Biomedicine Parc Científic de Barcelona Josep Samitier 1 5 Barcelona 08028 Spain Barcelona Supercomputing Centre Jordi Girona 31 Edifici Torre Girona Barcelona 08034 Spain Departament de Bioquímica Facultat de Biología Avgda Diagonal 647 Barcelona 08028 Spain

School of Pharmacy and Centre for Biomolecular Sciences University of Nottingham NG7 2RD UK

Section de Mathématiques Swiss Federal Institute of Technology CH 1015 Lausanne Switzerland

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