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synopsisThe predominant role of van der Waal interactions in determining the helical conformations of a simple synthetic linear polymer, as well as helical polypeptides, was pointed out in systematic studies by Liquori et a1.V In the case of homopolypeptides the conformational analysis carried out on the basis of a simple semiempirical function describing the van der Waal pairwise interactions between the non directly bonded atoms lead to the conclusion that only five helices are allowed (Ra, 8, y, 6, L01).%3In view of the close similarities with poly-Galanine, we have investigated by x-ray and conformational analysis the molecular conformation of poly(S-lactic acid) which has recently been described by Kleine and Kleine4 and Schuls and Schwaab5 and studied in solution by Goodman and D'Alagni.6 In fact, this polymer may be related to the polypeptide by the interchange of a peptide bond with ester bond along the main chain. This operation is expected to involve only a relatively small change in the steric interaction within the possible helical conformation, but obviously rules out any possibility of hydrogen bonding.

Cylindrical coordinates and symmetries of regular enantiomeric sequences were derived on the basis of eigenvalue-eigenvectors solns. to the Eyring-transformation matrix, and were used to show that the general structure of conformationally equiv. enantiomers was a ring. Helical structures could be formed in the case of quasi-conformational equivalence between the monomeric units. For regular L,D copolypeptides, these helical structures were stabilized by both van der Waals and H bond interactions, and were more stable than the α-helix in the absence of configurational disorder

The validity of a theoretical nearest-neighbor model based on conformational energy calculations, for translating the deterministic fluctuations of DNA base sequences in superstructural elements, is tested on the electrophoretic data of 450 multimeric, duplex oligonucleotides with different sequence, periodicity, and complexity, corresponding to all the experimental data so far published. An accurate semiempirical linear relation between the gel electrophoretic retardation and the dispersion of the theoretical curvature was found which allows a prediction of electrophoretic anomalies of DNA tracts, e.g., the cyclic permutation gel assays, with great confidence. Such a pattern of agreement allows the interpretation of the gel electrophoresis retardation as due to an increase of activation energy required in straightening the DNA axis.

A theoretical model for predicting nucleosome thermodynamic stability in terms of DNA sequence is advanced. The model is based on a statistical mechanical approach, which allows the calculation of the canonical ensemble free energy involved in the competitive nucleosome reconstitution. It is based on the hypothesis that nucleosome stability mainly depends on the bending and twisting elastic energy to transform the DNA intrinsic superstructure into the nucleosomal structure. The ensemble average free energy is calculated starting from the intrinsic curvature, obtained by integrating the dinucleotide step deviations from the canonical B-DNA and expressed in terms of a Fourier series, in the framework of first-order elasticity. The sequence-dependent DNA flexibility is evaluated from the differential double helix thermodynamic stability. A large number of free-energy experimental data, obtained in different laboratories by competitive nucleosome reconstitution assays, are successfully compared to the theoretical results. They support the hypothesis that the stacking energies are the major factor in DNA rigidity and could be a measure of DNA stiffness. A dual role of DNA intrinsic curvature and flexibility emerges in the determination of nucleosome stability. The difference between the experimental and theoretical (elastic) nucleosome-reconstitution free energy for the whole pool of investigated DNAs suggests a significant role for the curvature-dependent DNA hydration and counterion interactions, which appear to destabilize nucleosomes in highly curved DNAs. This model represents an attempt to clarify the main features of the nucleosome thermodynamic stability in terms of physical-chemical parameters and suggests that in molecular systems with a large degree of complexity, the average molecular properties dominate over the local features, as in a statistical ensemble.

The energy of DNA deformation plays a crucial and active role in its packaging and its function in the cell. Considerable effort has gone into developing methodologies capable of evaluating the local sequence-directed curvature and flexibility of a DNA chain. These studies thus far have focused on DNA constructs expressly tailored either with anomalous flexibility or curvature tracts. Here we demonstrate that these two structural properties can be mapped also along the chain of a “natural” DNA with any sequence on the basis of its scanning force microscope (SFM) images. To know the orientation of the sequence of the investigated DNA molecules in their SFM images, we prepared a palindromic dimer of the long DNA molecule under study. The palindromic symmetry also acted as an internal gauge of the statistical significance of the analysis carried out on the SFM images of the dimer molecules. It was found that although the curvature modulus is not efficient in separating static and dynamic contributions to the curvature of the population of molecules, the curvature taken with its direction (its sign in two dimensions) permits the direct separation of the intrinsic curvature from the flexibility contributions. The sequence-dependent flexibility seems to vary monotonically with the chain's intrinsic curvature; the chain rigidity was found to modulate as its local thermodynamic stability and does not correlate with the dinucleotide chain rigidities evaluation made from x-ray data by other authors.

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