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Biomedical subjects

R Lavery

Publications and source records attributed to R Lavery.

At least 91 records · Page 5Linked to original sources
PubMed1986

The flexibility of the nucleic acids: (II). The calculation of internal energy and applications to mononucleotide repeat DNA.

Results concerning the flexibility of mononucleotide repeat DNA are presented using a novel methodology, denoted "SIR", to describe continuous changes in the structure of the nucleic acid. This methodology, combined with internal energy calculations and analytical energy gradients allows us to determine optimal conformations of poly(dG).poly(dC) and poly (dA).poly(dT) in both the A and B forms, taking into account the influence of the solvent medium and explicit counterions. Subsequently, several different types of distorsion of these optimal structures are investigated. It is shown that excellent correlation with experimental results concerning coupled changes in structural variables is obtained and several new correlations are also detected.

DNA↗
PubMed1986

The flexibility of the nucleic acids: (III). The interaction of an aliphatic diamine, putrescine, with flexible B-DNA.

A theoretical modelling of the interaction of putrescine (H3+N-(CH2)4-(+NH3) with DNA is carried out, introducing two new features which make the simulation of this interaction considerably more realistic. Firstly, the DNA to which putrescine is bound is fully flexible and thus able to respond to the distorting influence of the ligand. Secondly, the effect of changing the ratio of DNA base pairs per bound ligand is explicitly modelled. In this way, we have been able to confirm the experimentally known preference of putrescine binding with AT base pairs in B-DNA, but we also show, through the new features introduced, that the nature of the binding site of the ligand and the resulting impact on DNA conformation is strongly modified by the ligand binding density.

Binding Sites↗
PubMed1986

Binding of non-intercalating antibiotics to B-DNA: a theoretical study taking into account nucleic acid flexibility.

A detailed theoretical study has been made for five antibiotics which all bind selectively to AT sequences in the minor groove of B-DNA: SN-18071, NSC-101327, distamycin-2, distamycin-3 and netropsin. The optimal complexes were found for systems in which the flexibility of DNA, as well as that of the antibiotics, was taken into account. Explicit, mobile counterions and a dielectric function modelling aqueous solution were also included. The binding geometries of the most strongly interacting antibiotics, distamycin-3 and netropsin, are compared in considerable detail and it is shown that notable differences exist between them. The results for netropsin are also discussed in the light of recent disagreements concerning its exact binding location within DNA.

Anti-Bacterial Agents↗
PubMed1985

The dependence of the surface electrostatic potential of B-DNA on environmental factors.

The electrostatic potential of B-DNA is calculated on its surface envelope for two homopolymeric base pair sequences using models representing the effects of both counterion binding and of aqueous solution. The influence of these two factors on the resulting potentials is established and the significance of calculations which omit such effects is discussed.

Base Composition↗
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

A new theoretical index of biochemical reactivity combining steric and electrostatic factors. An application to yeast tRNAPhe.

A new theoretical index of the chemical reactivity of sites within macromolecules is developed, which combines both steric and electrostatic factors. It is applied to the study of yeast tRNAPhe and the results obtained are compared with known experimental reactivities. A comparison indicates the superiority of the new index over the sole use of the surface accessibility.

Adenine↗
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

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↗
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↗
PubMed1981

The molecular electrostatic potential, steric accessibility and hydration of Dickerson's B-DNA dodecamer d(CpGpCpGpApApTpTpCpGpCpG).

The paper presents the results of computation of the electrostatic potential and steric accessibility of the B-DNA self-complementary dodecamer CGCGAATTCGCG following the geometry of the recent single crystal structure of Dickerson et al. This structure shows significant variations from classical B-DNA; their influences on the calculated properties are discussed. The results are related to general features of hydration of the crystal. A particularly significant general finding concerns the greater negative potential in the center of the oligonucleotide helix than at its extremities. This will be a general feature of such short helices, independent of their base sequence. It may have important implications for the reactivity of DNA oligomers.

Calorimetry↗