title: Unraveling the sequence-dependent polymorphic behavior of d(CpG) steps in B-DNA.
abstract: We have made a detailed study of one of the most surprising sources of polymorphism in B-DNA: the high twist/low twist (HT/LT) conformational change in the d(CpG) base pair step. Using extensive computations, complemented with database analysis, we were able to characterize the twist polymorphism in the d(CpG) step in all the possible tetranucleotide environment. We found that twist polymorphism is coupled with BI/BII transitions, and, quite surprisingly, with slide polymorphism in the neighboring step. Unexpectedly, the penetration of cations into the minor groove of the d(CpG) step seems to be the key element in promoting twist transitions. The tetranucleotide environment also plays an important role in the sequence-dependent d(CpG) polymorphism. In this connection, we have detected a previously unexplored intramolecular C-H···O hydrogen bond interaction that stabilizes the low twist state when 3'-purines flank the d(CpG) step. This work explains a coupled mechanism involving several apparently uncorrelated conformational transitions that has only been partially inferred by earlier experimental or theoretical studies. Our results provide a complete description of twist polymorphism in d(CpG) steps and a detailed picture of the molecular choreography associated with this conformational change.
authors.affiliation: Joint BSC-CRG-IRB Research Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, Barcelona 08028, Spain.
authors.forename: Pablo Daniel
authors.identifier: http://orcid.org/0000-0002-5927-372X
authors.initials: PD
authors.lastname: Dans
authors.affiliation: Joint BSC-CRG-IRB Research Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, Barcelona 08028, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Faustino
authors.affiliation: Joint BSC-CRG-IRB Research Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, Barcelona 08028, Spain.
authors.forename: Federica
authors.initials: F
authors.lastname: Battistini
authors.affiliation: Bases Moléculaires et Structurales des Systèmes Infectieux, Univ. Lyon I/CNRS UMR 5086, IBCP, 7 Passage du Vercors, Lyon 69367, France.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Zakrzewska
authors.affiliation: Bases Moléculaires et Structurales des Systèmes Infectieux, Univ. Lyon I/CNRS UMR 5086, IBCP, 7 Passage du Vercors, Lyon 69367, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Lavery
authors.affiliation: Joint BSC-CRG-IRB Research Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, Barcelona 08028, Spain Departament de Bioquimica, Facultat de Biologia, Avgda Diagonal 647, Barcelona 08028, Spain modesto.orozco@irbbarcelona.org.
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
mesh_terms: D001483:Base Sequence; D002412:Cations / Q000737:chemistry; D018899:CpG Islands; D059371:DNA, B-Form / Q000737:chemistry*; D006860:Hydrogen Bonding; D009690:Nucleic Acid Conformation; D013816:Thermodynamics; D054159:Torsion, Mechanical
chemical_list: D002412:Cations; D059371:DNA, B-Form