| Mechanochemical study of NaDNA and NaDNA-netropsin fibers in ethanol-water and trifluoroethanol-water solutions Biophysical Journal, Volume 68, Issue 3, 1 March 1995, Pages 1050-1062 Z. Song, A. Rupprecht and H. Fritzsche Abstract Highly oriented calf-thymus NaDNA fibers, prepared by a wet-spinning method, were complexed with netropsin in ethanol-water and trifluoroethanol (TFE)-water solutions. The relative fiber length, L/L0, was measured at room temperature as a function of ethanol or TFE concentration to obtain information on the B-A conformational transition. The B-A transition point and transition cooperativity of the fibers were calculated. The binding of netropsin to NaDNA fibers was found to stabilize B form and to displace the B-A transition to higher ethanol concentration, as indicated by its elongational effect on the fiber bundles. An increased salt concentration was found to reduce netropsin binding. In netropsin-free ethanol solution, the dissociation of bound netropsin from the DNA fibers was observable. Pure B-NaDNA fibers were found to be more stable in TFE solution than in ethanol solution. This was interpreted as being due to a different steric factor and a larger polarity of TFE compared with ethanol, resulting in its smaller capacity to reduce the water activity and dielectric constant of the medium in the immediate vicinity of DNA fibers. Therefore, the effect of netropsin binding on the B-A transition of NaDNA fibers became less obvious in TFE solution. In another series of experiments, L/L0 was measured as a function of temperature to obtain information on the helix-coil transition, or melting, as well as the B-A transition of NaDNA and NaDNA-netropsin fibers. The melting temperature and helix-coil transition width were calculated from the melting curves. A phenomenological approach was used to describe the melting behavior of the fibers in and around the B-A transition region. The effect of netropsin on the melting of DNA fibers was attributed mainly to the stabilization of B-DNA and to a higher melting cooperativity in the B-DNA region. Abstract | PDF (12012 kb) |
| Optimization of Nucleic Acid Sequences Biophysical Journal, Volume 79, Issue 2, 1 August 2000, Pages 680-685 Ingrid Lafontaine and Richard Lavery Abstract Base sequence influences the structure, mechanics, dynamics, and interactions of nucleic acids. However, studying all possible sequences for a given fragment leads to a number of base combinations that increases exponentially with length. We present here a novel methodology based on a multi-copy approach enabling us to determine which base sequence favors a given structural change or interaction via a single energy minimization. This methodology, termed ADAPT, has been implemented starting from the JUMNA molecular mechanics program by adding special nucleotides, “lexides,” containing all four bases, whose contribution to the energy of the system is weighted by continuously variable coefficients. We illustrate the application of this approach in the case of double-stranded DNA by determining the optimal sequences satisfying structural (B–Z transition), mechanical (intrinsic curvature), and interaction (ligand-binding) properties. Abstract | Full Text | PDF (103 kb) |
| Significance of Ligand Tails for Interaction with the Minor Groove of B-DNA Biophysical Journal, Volume 81, Issue 3, 1 September 2001, Pages 1588-1599 Bernd Wellenzohn, Wolfgang Flader, Rudolf H. Winger, Andreas Hallbrucker, Erwin Mayer and Klaus R. Liedl Abstract Minor groove binding ligands are of great interest due to their extraordinary importance as transcription controlling drugs. We performed three molecular dynamics simulations of the unbound d(CGCGAATTCGCG) dodecamer and its complexes with Hoechst33258 and Netropsin. The structural behavior of the piperazine tail of Hoechst33258, which has already been shown to be a contributor in sequence-specific recognition, was analyzed. The simulations also reveal that the tails of the ligands are able to influence the width of the minor groove. The groove width is even sensitive for conformational transitions of these tails, indicating a high adaptability of the minor groove. Furthermore, the ligands also exert an influence on the B/B backbone conformational substate behavior. All together these results are important for the understanding of the binding process of sequence-specific ligands. Abstract | Full Text | PDF (300 kb) |
Copyright © 1996 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 71, Issue 6, 3344-3349, 1 December 1996
doi:10.1016/S0006-3495(96)79527-9
Research Article
V.I. Ivanov, L.E. Minchenkova, G. Burckhardt, E. Birch-Hirschfeld, H. Fritzsche and C. Zimmer
W. A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
The transition of the 14-meric deoxyoligonucleotide duplex d-(ACCCCCTTTTTTTG).d-(CAAAAAAAGGGGGT) from the B- to the A-conformation in water/trifluorethanol (TFE) solution was studied with the use of circular dichroism. An increase in the fraction of TFE induces a two-step B-A transition. In the first step, up to 73% TFE, the A-form is generated from the GC-rich part; in the second step, 73–82% TFE, the AT-rich part shifts to the A-form. By this we suggest the existence of a B/A junction near 73% TFE. Emergence of the B/A junction has been directly confirmed with the use of distamycin A and netropsin, ligands known to selectively bind to AT stretches of B-DNA. It can be shown that both ligands suppress formation of the A-form in the B-philic part. The free energy value for the B/A junction was estimated to be 2.1 kcal/mol, which agrees well with known data for polymeric DNAs. The obtained results may have biological relevance in connection with recently published x-ray data about the occurrence of the B/A junction in the complex of DNA with reverse transcriptase of HIV.