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Biomedical subjects

B Pullman

Publications and source records attributed to B Pullman.

At least 55 records · Page 3Linked to original sources
PubMed1984

The solvation contribution to the binding energy of DNA with non-intercalating antibiotics.

The influence of the solvent on the binding energies to DNA of six non-intercalating antibiotics - netropsin, distamycin-3, distamycin-2, SN 18071, berenil and stilbamidine - is evaluated by combining the effect of the first hydration shell with that of bulk water. The first effect is computed by a methodology based on a spherical/point dipole model of water and limited to electrostatic interaction energies. Hydration shells are obtained which are energy optimized with respect to both water-solute and water-water interactions for the complexes and for the isolated DNA oligomers and ligands. The method allows even very large complexes to be studied in reasonable computation times. The second effect is introduced via a cavity treatment. It is shown that if the vacuum interaction energies already predict correctly the preference of the ligands for the minor groove of AT sequences of B-DNA, the introduction of the solvation effect is indispensable for reproducing the order of affinity of the ligands and for bringing the values of the complexation energies into close agreement with experimental data.

Anti-Bacterial Agents↗
PubMed1984

Proton NMR study of the B----Z transition of d(CGm5CG)2 and d(CGm5CGCG)2: theory and experiment.

The magnetic shielding produced by the double helix in a B-DNA and a Z-DNA conformation is calculated for each non exchangeable proton of the oligodeoxynucleotides d(CGm5CG)2 and d(CGm5CGCG)2. The differences between the values obtained for the two helical forms are in good agreement with the variations of chemical shift measured when the salt concentration of the solution is changed from 0.1 M to 2 or 4 M. The analysis of the theoretical chemical shift variations shows that the large upfield shift observed for some of the protons of the cytidine residues is due to the sum of the ring current and local magnetic anisotropy effects of the guanines of the two nearest neighbours residues.

Magnetic Resonance Spectroscopy↗
PubMed1984

A theoretical study of the nonintercalative binding of berenil and stilbamidine to double-stranded (dA-dT)n oligomers.

The nonintercalative binding of two diarylamidines , berenil and stilbamidine , to the minor groove of double-stranded (dA-dT)n oligomers in the B-DNA conformation was investigated by performing theoretical computations of their intermolecular interaction energies with the groove. The method consists of an additive procedure developed previously in this laboratory using empirical formulae based on ab initio computations. The objective was to assess the extent to which the particular structure of each diarylamidine bears on its binding mode and affinity to the minor groove. The results show that the intrinsically preferred configurations of the two compounds are markedly different. Owing to its slightly curved shape, berenil interacts with the groove predominantly through its concave side, the binding occurring principally with sites (O2, O1) belonging to two thymidines on the opposite strands. The binding of stilbamidine involves a more limited number of hydrogen-bonding interactions, although an appreciably large number of interatomic distances between its hydrogens and sites on the groove (O2, N3, O1) falls in the range 2.7-3.1 A. Each side of stilbamidine with respect to its long axis faces a distinct strand of DNA. The importance of the electrostatic contribution of the binding energy of the two diarylamidines is underlined. Preferential binding of berenil rather than of stilbamidine occurs only at the level of a complete helical turn of phosphates in (dA-dT)n. The energy difference increases significantly upon further buildup of phosphates. These results can be interpreted in terms of the molecular electrostatic potential in the grooves.

Amidines↗
PubMed1983

Theoretical studies of the selective binding to DNA of two non-intercalating ligands: netropsin and SN 18071.

A theoretical study of the binding to DNA of netropsin and a bisquaternary ammonium heterocycle, SN 18071, is undertaken with an energy minimizing program based on empirical potential functions. The positioning of the ligand is achieved by force and torque calculations and its internal flexibility is taken into account. The binding preference of both drugs studied for the AT minor groove of B-DNA is shown to depend on both the electrostatic potential generated by the base sequence and the quality of the steric fit of the ligand in the groove. Ligand-DNA hydrogen bonds are shown to aid binding, but not to be essential in establishing binding preferences.

Amino Acid Sequence↗
PubMed1983

A theoretical evaluation of the effect of netropsin binding on the reactivity of DNA towards alkylating agents.

The effect of netropsin binding on the electrostatic potential of DNA reactive sites is presented. Calculations are performed for atoms N7 and O6 of guanine, N3 and N7 of adenine of model, 25 base pair long, DNA-netropsin complexes. An important weakening of the potential is found spreading along all the oligonucleotide chain studied. The results are discussed in connection with the inhibitory effect of a related ligand, distamycin A, on DNA methylation.

Alkylating Agents↗
PubMed1983

Theoretical NMR study of the pre-melting transition in the d-(CGCGAATTCGCG) and d-(CGCGTATACGCG) self-complementary duplexes.

The difference between their shielding in a B-DNA duplex and in the single strand having the same conformation has been calculated for all base protons of the dodecamers d-(CGCGAATTCGCG) and d-(CGCGTATACGCG). The calculated chemical shift variations reproduce the qualitative features of the shifts which occur during the pre-melting of the helices. This agreement shows that the pre-melting mechanism consists mainly of a lengthening of the hydrogen bonds between the two strands (in line opening) and that the conformation of the ribophosphate backbone and the orientation of the bases do not undergo major modifications during the first step of the melting.

Base Sequence↗
PubMed1983

The electrostatic field of the component units of DNA and its relationship to hydration.

The electrostatic fields of the subunits of DNA are presented and compared with the corresponding electrostatic potentials. Differences are observed between these two properties, due to their different dependence on distance, which are of considerable interest since, whereas the potential may be used in studying the reactivity of molecules towards charged species, the field can be a similar guide to attack by neutral, dipolar molecules such as water. It is demonstrated, for the example of the purine and pyrimidine bases, that the field may indeed be used to detect preferential hydration sites.

Adenine↗
PubMed1983

Electrostatics of Polymorphic DNA.

The molecular electrostatic potential (MEP) and the molecular electrostatic field (MEF) are associated with significantly different patterns of distribution in the nucleic acids and their constituents. In particular, a) while the values of the minimal potentials at the reactive sites of the bases or at the phosphates increase manyfold when going from the subunits to the double helix, the values of the field undergo only very small changes under the same circumstances and b) while the deepest potentials are located in the grooves of the double helix, the greatest fields are concentrated on the phosphates of the backbone. They are also influenced differently by such environmental factors as counterion screening: while the absolute values of the potentials are profoundly reduced, the fields are increased with respect to those of the unscreened acids. MEP and MEF also govern the electrostatics of interaction of DNA with different types of species. The MEP being of particular significance in this respect for interaction with cations and the MEF for the association with neutral dipolar molecules. A number of examples are given to illustrate the significance of this situation for different conformers of DNA.

DNA↗
PubMed1982

The electrostatic field of DNA: the role of the nucleic acid conformation.

Calculations of the electrostatic field of DNA in two very different double helical conformations, A and Z, are reported and compared with the results previously obtained for B-DNA. Striking contrasts between these fields and the associated electrostatic potentials are brought into evidence. One of the major differences is that while the deepest potentials are generally located in the grooves of DNA, the strongest fields are associated with the phosphate groups. The results of screening the nucleic acids by counterions are also presented.

DNA↗
PubMed1982

Two aspects of DNA polymorphism and microheterogeneity: molecular electrostatic potential and steric accessibility.

Polymorphism and microheterogeneity of DNA appear today as being capable of having important biological consequences. This paper presents a synthetic view of two major properties of the main known forms of DNA (A, B, alternating B, C, D and Z), namely their molecular electrostatic potentials and steric accessibilities. Variations in these properties are explained in terms of the conformational changes involved and deductions are drawn concerning their influence on the interactive properties of DNA with external agents.

Base Composition↗
PubMed1982

Intrinsic electrostatic properties and base sequence effects in the structure of oligonucleotides.

Molecular electrostatic potentials and steric accessibilities are calculated for Dickerson's dodecanucleotide CGCGAATTCGCG and compared with those for the 'inverted' sequence TATAGGCCTATA. The results are used to distinguish between properties due to base sequence (the location of the deepest potential minimum in the minor groove of A-T sequences and in the major groove of G-C sequences) and those due to the finite length of the oligonucleotide (location of the deepest potential in the central part of the oligonucleotide).

Base Sequence↗
PubMed1981

The molecular electrostatic potential and steric accessibility of A-DNA.

The molecular electrostatic potential and steric accessibility of A-DNA are computed for base sequences (dG.dC)n and (dA.dT)n. An interpretation of the results in terms of the structure of A-DNA is provided and differences with respect to other forms of DNA, namely B-DNA and Z-DNA, are discussed.

Base Sequence↗