title: The intramolecular impact to the sequence specificity of B-->A transition: low energy conformational variations in AA/TT and GG/CC steps.
abstract: It is well known, that local B--> A transformation in DNA is involved in several biological processes. In vitro B<--> A transition is sequence-specific. The physical basis of this specificity is not known yet. Here we analyze the effect of intramolecular interactions on the structural behavior of the GG/CC and AA/TT steps. These steps exemplify sequence specific bias to the B- or A-form structure. Optimization of potential energy of the molecular systems composed of an octanucleotide, neutralized by Na(+) and solvated with TIP3P water molecules in rectangular box with periodic boundary conditions gives the statistically representative sets of low energy structures for GG/CC and AA/TT steps in the middle of the diverse flanking sequences. Permissible 3D variations of GG/CC and AA/TT, and correlation of the relative motion of base pairs in these steps were analyzed. AA/TT step permits high variability for low energy conformers in the B-form DNA and small variability for low energy conformers in the A-form DNA. In contrast GG/CC step permits high variability for low energy conformers in the A-form DNA and small variability for low energy conformers in the B-form DNA. The relative motion of base pairs in GG/CC step is high correlated, while in AA/TT step this correlation is notably less. Atom-atom interactions inside-the-step always favors the B-form and their component - stacking interactions (atom-atom interactions between nucleic bases) is crucial for the duplex stabilization. Formation of the A-form for both steps is a result of interactions with the flanking sequences and water-cation environment in the box. The average energy difference between conformations presenting B-form and A-form for the GG/CC step is high, while for the AA/TT step it is rather low. Thus, intramolecular interactions in GG/CC and AA/TT steps affect the possible conformational diversity ("conformational entropy") of the A- and B- type structures of DNA step. This determines the known bias of the A-form DNA depending on the enrichment of sequences with GG/CC. If structural tuning during the process of protein-DNA complex formation lead to the local B--> A transformation of DNA, it is largely directed by high conformational diversity of GG/CC step in the A-form. In such a case the presence in the target site of both kinds of examined steps ensures the reversible character of ligand binding.
authors.affiliation: Engelhardt Institute of Molecular Biology RAS, Vavilov str., 32, 119991 Moscow, Russia. imb_irina@rambler.ru.
authors.forename: I A
authors.initials: IA
authors.lastname: Il'icheva
authors.forename: P K
authors.initials: PK
authors.lastname: Vlasov
authors.forename: N G
authors.initials: NG
authors.lastname: Esipova
authors.forename: V G
authors.initials: VG
authors.lastname: Tumanyan
mesh_terms: D001483:Base Sequence; D019281:Dimerization; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry* / Q000235:genetics; D011506:Proteins / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D009711:Nucleotides; D011506:Proteins