A molecular mechanical model to predict the helix twist angles of B-DNA

Abstract

We present here a model for the prediction of helix twist angles in B-DNA, a model composed of a collection of torsional springs. Statistically averaged conformational energy calculations show that, for a specified basepair step, the basepair-basepair conformational energy is quadratically dependent on the helix twist angle, so the calculations provide the spring parameters for the basepair-basepair interactions. Torsional springs can also be used to model the effects of the backbone on the helix twist, and the parameters for those springs are derived by fitting the model to experimental data. The model predicts a macroscopic torsional stiffness and a longitudinal compressibility (Young's modulus) which are both in good agreement with experiment. One biological consequence of the model is examined, the sequence specificity of the Eco RI restriction endonuclease, and it is shown that the discriminatory power of the enzyme receives a substantial contribution from the energetic cost of torsional deformations of the DNA when wrong sequences are forced into the enzyme binding site.

A common structural feature in promoter sequences ofE. coli

“…How can we explain the apparently random locations of these structures within the promoter in terms of biological activity? Numerous papers have discussed the possibility that local variations in DNA geometry can modulate protein-DNA interactions (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)28,29). Perhaps consensus structures serve as pause signals to RNA polymerase.…”

“…In summary, we have shown that promoters in E. coli contain homologous structural regions with a frequency that is substantially greater than that with which homologous structures are found in structural genes or random sequence DNA. It has often been argued (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)28,29) that particular kinds of DNA structures may play a role in modulating the interactions between proteins and DNA. Since hard evidence for this belief is still lacking, it is important to identify specific structures and the set of associated sequences that might be involved in such modulation.…”

“…DNA twisting is often modeled by assuming that the torsional energy is proportional to the square of the deformation twist angle (9,11,25; see 9 for references to much of the experimental literature), so s2 is a measure of deformation energy. We have chosen a cutoff of s2 -5.0 deg2, corresponding to a deformation energy that is roughly equal to kT, the available thermal energy (9,11,25).…”

“…Several recent investigations (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) have examined the relationships between DNA sequence and the variations in the local geometry of the double helix. The results of these studies have been compared to experimental examinations of the sequence-dependence of DNA bending (14)(15)(16)(17)(18) and used to look for systematic variations of DNA structure in both prokaryotes (19)(20)(21) and eukaryotes (22).…”

“…We have recently reported the results of conformational energy calculations on the relationship between sequence and structure in DNA, presenting algorithms for the prediction of both helix twist angle and basepair roll angle (9,11). The advantages of this approach are that every atom of each base is explicitly represented and that a large region of conformational space is sampled.…”