Rabi Majumdar

Sequence Directed Flexibility of DNA and the Role of Cross-strand Hydrogen Bonds

Persistence length and torsional rigidity for different B-DNA sequences have been calculated by analysing crystal structure database. The values of these parameters for mixed sequence DNA are in good agreement with those estimated by others. Persistence lengths for the homopolymeric sequences, namely poly(dA).poly(dT) and poly(dG).poly(dC), are significantly large compared to those of others as expected from the inability of these sequences to form nucleosome under normal conditions. The heteropolymeric sequences poly(dA-dC).poly(dG-dT) and poly(dG-dC).poly(dG-dC), on the other hand, have smaller persistence lengths. This implies larger flexibility of the d(AC).d(GT), d(CA).d(TG), d(GC).d(GC) and d(CG).d(CG) doublets, some of which constitute the genetic disease forming triplet repeats d(CTG).d(CAG) and d(CGG).d(CCG). Thus it is expected that these triplet repeat sequences are also flexible and wrap around the histone octamer efficiently. Persistence length calculations also indicate larger flexibility for these triplet repeat sequences. Furthermore, our computations reveal that the rigidity of a given DNA sequence is controlled by its ability to form cross-strand bifurcated hydrogen bonds between the successive base pairs. Molecular orbital calculations suggest that these hydrogen bonds are generally extended with bond lengths around 3A.

Melting characteristics of highly supercoiled DNA

The effect of high supercoil densities on the melting characteristics of a supercoiled DNA has been studied. It is found that although the melting temperature increases abruptly on converting a linear DNA merely into the relaxed circular form, it falls back substantially at high supercoil densities. It is further predicted, in such cases, that the number of melted base pairs should be significantly enhanced even at the physiological temperature, which may facilitate the binding of other molecules to the highly supercoiled DNA.

Nucleosomal positioning and genetic divergence study based on DNA flexibility map.

Abstract Based on worm like chain model, DNA structural parameters—tilt, roll and rise, derived from crystallographic database have been used to determine the flexibility of DNA that regulates the nucleosomal translational positioning. Theoretically derived data has been compared to the experimental values available in Ioshikhes and Trifonovs database. The methodology has been extended to determine the flexibility of 18S rRNA genome in eukarya, where yeast shows a distinct difference when compared with mammals like human, mouse and rabbit.

Ligand binding isotherm for DNA in the presence of supercoil-induced non-B form: a theoretical analysis

A binding isotherm in the form of a modified McGhee-Von Hippel equation is proposed, on the basis of thermodynamical considerations, to include the non-cooperative binding of extended ligands to supercoiled DNA, where a stretch of non-B form may be present under superhelical stress. It is then studied, on the basis of a non-linear Scatchard plot, how the presence of an intercalating ligand can relax the supercoiled molecule and thus destabilise the non-B stretch, which may be recognised by the existence of a significant kink in the Scatchard plot.

Theory of a supercoil-induced B-Z transition in closed circular DNA

Abstract An expression for the supercoiling free energy was obtained for a covalently closed circular B DNA in terms of the elastic parameters of the macromolecule. It is well known that this freeenergy source may induce conformational changes, such as the B-Z transition, under physiological conditions. As an extension of our earlier work, a more realistic theory of the supercoil-induced B-Z transition in a Z -transformable stretch, cloned into the closed circular DNA, was developed on the basis of statistical thermodynamics. The results clearly indicate that the transition is cooperative at a critical supercoil density, which may be followed by a continuous elongation of the Z -stretch with increasing supercoiling. The results are found to be in very good agreement with the available experimental data.

Computational approach to the study of supercoil-induced structural polymorphism in DNA

Abstract The superhelical strain in a closed circular B DNA molecule may be relieved at the cost of local conformational transitions to non-B forms wherever possible. Some of these transitions, such as the supercoil-induced B-Z transition in a short purine-pyrimidine stretch, are known to be highly cooperative and can be described in terms of a two-state approximation for the relevant chain partition function. How the presence of DNA-binding ligands may affect such transitions within the supercoiled molecule has been analysed. The result of a preliminary investigation into the effect of sharp bends in the supercoiled DNA structure is also reported.