Collective motion in DNA and its role in drug intercalation

The effects of collective motion in DNA as reflected by resonance coupling among its intact segments have been discussed for both linear and circular DNA molecules. The results indicate that due to the effects of this kind of internal collective motion, the energy will be at times highly concentrated at some spots. As a result of the overfocus of energy, the stress built up along the direction of hydrogen bonds between complementary base pairs will be dramatically increased, rupturing a series of consecutive hydrogen bonds simultaneously and resulting in a suddenly free jerk, such that the DNA molecule will undergo a local “quake.” The “hole” formed by this kind of quake‐like motion will be large enough for bulky drugs to gain entrance and intercalate into DNA. Even for smaller drugs, this local quake‐like motion can also provide a significant mode of entry for intercalation. Energy minimizations carried out for DNA–drug complexes indicate that, for most drugs, a distortion or disruption of 2 to 4 base pairs occurs at the intercalation site in DNA molecules.

[1]  P. Painter,et al.  Low-frequency modes in the Raman spectra of proteins. , 1982, Biopolymers.

[2]  P. Luisi,et al.  A mechanical model for the half-of-the-sites reactivity of oligomeric enzymes. , 1974, Biophysical chemistry.

[3]  L. Finegold,et al.  Vibrational states of the biopolymer polyglycine II: theory and experiment , 1975, Science.

[4]  E. Westhof,et al.  Covalent binding of a carcinogen as a probe for the dynamics of deoxyribonucleic acid. , 1985, Biochemistry.

[5]  P. Painter,et al.  Low-frequency modes in the raman spectrum of DNA. , 1981, Biopolymers.

[6]  N. Kallenbach,et al.  Base-pair opening and closing reactions in the double helix. A stopped-flow hydrogen exchange study in poly(rA).poly(rU). , 1979, Journal of molecular biology.

[7]  E. Prohofsky,et al.  Low-frequency lattice mode predictions in A-DNA compared to experimental observations and significance for A-to-B conformation change. , 1984, Biopolymers.

[8]  K. Chou,et al.  The biological functions of low‐frequency vibrations (phonons). VI. A possible dynamic mechanism of allosteric transition in antibody molecules , 1987, Biopolymers.

[9]  H. M. Sobell.  Actinomycin and DNA transcription. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[10]  G Careri,et al.  Statistical time events in enzymes: a physical assessment. , 1975, CRC critical reviews in biochemistry.

[11]  G. S. Manning.  Breathing and bending fluctuations in DNA modeled by an open‐base‐pair kink coupled to axial compression , 1983, Biopolymers.

[12]  K. Chou,et al.  The biological functions of low-frequency vibrations (phonons). 4. Resonance effects and allosteric transition. , 1984, Biophysical chemistry.

[13]  K. G. Brown,et al.  Conformationally dependent low-frequency motions of proteins by laser Raman spectroscopy. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Fiel,et al.  Binding of meso-tetra (4-N-methylpyridyl) porphine to DNA. , 1980, Nucleic acids research.

[15]  Peter A. Kollman,et al.  AMBER: Assisted model building with energy refinement. A general program for modeling molecules and their interactions , 1981 .

[16]  P. A. W. Lewis,et al.  A Pseudo-Random Number Generator for the System/360 , 1969, IBM Syst. J..

[17]  K. Chou,et al.  Low-frequency vibrations of DNA molecules. , 1984, The Biochemical journal.

[18]  P. Painter,et al.  The low-frequency Raman spectrum of an antibody molecule: bovine IgG. , 1979, Biopolymers.

[19]  K. Chou,et al.  The flexibility during the juxtaposition of reacting groups and the upper limits of enzyme reactions. , 1981, Biophysical chemistry.

[20]  L. Genzel,et al.  Low‐frequency Raman spectra of lysozyme , 1976, Biopolymers.

[21]  K. Chou,et al.  Origin of low-frequency motions in biological macromolecules. A view of recent progress in the quasi-continuity model. , 1986, Biophysical chemistry.