title: μABC: a systematic microsecond molecular dynamics study of tetranucleotide sequence effects in B-DNA.
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.
authors.affiliation: Section de Mathématiques, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Pasi
authors.affiliation: Section de Mathématiques, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland john.maddocks@epfl.ch.
authors.forename: John H
authors.initials: JH
authors.lastname: Maddocks
authors.affiliation: Department of Chemistry, Wesleyan University, Middletown, CT 06459, USA.
authors.forename: David
authors.initials: D
authors.lastname: Beveridge
authors.affiliation: Departments of Chemistry and Physics, Louisiana Tech University, Ruston, LA 71270, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Bishop
authors.affiliation: BioMaPS Institute and Deptartment of Chemistry and Chemical Biology, Rutgers University, 610 Taylor Road, Piscataway, NJ 08854-8087, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Case
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Skaggs 307, Salt Lake City, UT 84112, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cheatham
authors.affiliation: 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.
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Dans
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi 110016, India.
authors.forename: B
authors.initials: B
authors.lastname: Jayaram
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 166 10 Praha 6, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Lankas
authors.affiliation: School of Pharmacy and Centre for Biomolecular Sciences, University of Nottingham, NG7 2RD, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Laughton
authors.affiliation: Section de Mathématiques, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mitchell
authors.affiliation: Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Roman
authors.initials: R
authors.lastname: Osman
authors.affiliation: 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.
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
authors.affiliation: 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.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pérez
authors.affiliation: Section de Mathématiques, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Daiva
authors.initials: D
authors.lastname: Petkevičiūtė
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic.
authors.forename: Nada
authors.initials: N
authors.lastname: Spackova
authors.affiliation: 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.
authors.forename: Jiri
authors.initials: J
authors.lastname: Sponer
authors.affiliation: Bases Moléculaires et Structurales des Systèmes Infectieux, CNRS UMR 5086/Université Lyon I, IBCP, 7 Passage du Vercors, 69367 Lyon, France.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Zakrzewska
authors.affiliation: Bases Moléculaires et Structurales des Systèmes Infectieux, CNRS UMR 5086/Université Lyon I, IBCP, 7 Passage du Vercors, 69367 Lyon, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Lavery
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D059371:DNA, B-Form / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation
chemical_list: D059371:DNA, B-Form