Electrostatic potentials of E.coli genome DNA

Distribution of electrostatic potential of the complete sequence of E. coli genome was calculated. Comparative analysis of electrostatic patterns for 359 promoter and nonpromoter nucleotide sequences was carried out. It is found that nonpromoter regions are characterized by more homogeneous distribution of electrostatic potential with no common specific elements. Electrostatic patterns of promoter DNAs can be specified due to the presence of some distinctive motifs which may be involved as promoter signal elements in RNA-polymerase-promoter recognition.     

Electrostatic interactions in sperm whale myoglobin. Site specificity, roles in structural elements, and external electrostatic potential distributions

The electrostatic free energy contribution to the stability of sperm whale ferrimyoglobin was evaluated according to the static accessibility modified Tanford-Kirkwood model. The electrostatic free energy contribution of each distinct structural element was divided into one term arising from interactions between it and other elements (interelemental) and another from interactions within the particular element itself (intraelemental). At pH 7 the majority of the terms were found to be stabilizing. The interelemental terms are the dominant ones for most structural elements. The small interelemental terms of the C and D helices are compensated by large intraelemental interactions which stabilize these short helices. Perturbations in pH can be accommodated by the structural elements through a redistribution of stabilizing and destabilizing interactions. The electrostatic potentials calculated at the surface of the protein indicate that the internal compensation of local potentials achieved during folding results in a generally neutral protein-solvent interface save for two distinct areas of nonzero potential. The accessibility of each charged atom to solvent was analyzed in terms of the surface area lost to charged, polar and nonpolar atoms separately. The net solvent accessibility lost parallels closely that lost to nonpolar atoms alone, indicating a specific role for nonpolar atoms in defining dielectric shielding of charged atoms, aside from their participation in the well-known hydrophobic interactions.     

The ecology of the genome - mobile DNA elements and their hosts

The genomes of multicellular eukaryotes provide information that determines the phenotype. However, not all sequences in the genome are required for this purpose. Other sequences are often selfish in their actions and interact in complex ways. Here, an analogy is developed between the components of the genome, including mobile DNA elements, and an ecological community. Unlike ecological communities, however, the slow rates at which genomes change allow us to reconstruct patterns of interaction that stretch back tens or hundreds of millions of years.     

Electrostatic interactions in proteins: Calculations of the electrostatic term of free energy and the electrostatic potential field

The pH-dependence of the electrostatic energy of interactions between titratable groups is calculated for some well studied globular proteins: basic pancreatic trypsin inhibitor, sperm whale myoglobin and tuna cytochrome c. The calculations are carried out using a semi-empirical appraach in terms of the macroscopic model based on the Kirkwood-Tanford theory. The results are discussed in the light of their physicochemical and biological properties. It was found that the pH-dependence of the electrostatic energy correlates with the III–IV transition of cytochrome c. The electrostatic field of the cysteine proteinase inhibitor, cystatin, was calculated in two ways. In the first one, the electrostatic field created by the pH dependent charges of the ionizable groups and peptide dipoles was calculated using the approach proposed. In the second one, the finite-difference method was used. The results obtained by the two methods are in overall agreement. The calculated field was discussed in terms of the binding of cystatin to papain.     

Electrostatic map of T7 DNA: comparative analysis of functional and electrostatic properties of T7 RNA polymerase-specific promoters

The entire T7 bacteriophage genome contains 39937 base pairs (Database NCBI RefSeq N1001604). Here, electrostatic potential distribution around double helical T7 DNA was calculated by Coulomb method using the computer program of Sorokin A.A. (lptolik@gmail.com). Electrostatic profiles of 17 promoters recognized by T7 phage-specific RNA polymerase were analyzed. It was shown that electrostatic profiles of all T7 RNA polymerase-specific promoters can be characterized by distinctive motifs which are specific for each promoter class. Comparative analysis of electrostatic profiles of native T7 promoters of different classes demonstrates that T7 RNA polymerase can differentiate them due to their electrostatic features.     

Mobile dispersed repeated DNA elements in the Drosophila genome

The molecular and cytogenetic organizations of 19 nonhomologous dispersed repeated sequence families were studied in 15 different laboratory strains of Drosophila melanogaster. Elements from each of the families appear to undergo transposition within the Drosophila genome, because there were striking differences in both the number and chromosomal locations of these elements between strains. A significant fraction (greater than 1%) of Drosophila DNA therefore has an unstable genomic organization. Each middle repetitive family exhibited similar variations in the chromosomal distribution of elements between the strains. Although the movements of these elements are not limited to a small number of genomic sites, there are chromosomal regions where elements from the different dispersed repeated DNA families appear to be clustered. The locations of such preferred integration sites are different in each of the D. melanogaster strains examined.     

MITOMAP: a human mitochondrial genome database.

We have developed a comprehensive database (MITOMAP) for the human mitochondrial DNA (mtDNA), the first component of the human genome to be completely sequenced [Anderson et al. (1981) Nature 290, 457-465]. MITOMAP uses the mtDNA sequence as the unifying element for bringing together information on mitochondrial genome structure and function, pathogenic mutations and their clinical characteristics, population associated variation, and gene- gene interactions. As increasingly larger regions of the human genome are sequenced and characterized, the need for integrating such information will grow. Consequently, MITOMAP not only provides a valuable reference for the mitochondrial biologist, it may also provide a model for the development of information storage and retrieval systems for other components of the human genome.     

Docking on the DNA G-quadruplex: a molecular electrostatic potential study

The G-quadruplexes are four-stranded nucleic acid structures with guanine-rich sequences that play important biological roles in, for example, regulating telomerase association and activity. Recent evidence supports the hypothesis that the telomeric G-quadruplex DNA represents a target of novel anticancer drug medication. In this work, we present results of the molecular electrostatic potential (MEP), together with the HOMO and LUMO frontier orbitals, which are physical quantities of concern in the docking of compounds on the G-quadruplex. The calculations are performed in the frame of density functional theory at the B88LYP/6-31G* level of theory. Additional functionals that introduce dispersion effects were also taken into consideration. The MEP potential and electron density of the frontier molecular orbitals of the G-quadruplex exhibit topological deformations due to the coiled conformation of the compound when they are compared with the MEP and corresponding electron density of a DNA duplex with similar nucleic acid composition. The electrostatic active zone of the G-quadruplex is localized on the top part of the quadruplex structure where the MEP acquires the most negative values. Additional computations on a set of three daunomycins, a common anticancer drug for duplex DNA, indicate an electrostatic fastening between the quadruplex and the set of daunomycins. In this regard, the G-quadruplex electrostatic interactions favor the stacking of ligands. Finally, some implications on molecular drug design are briefly discussed.     

Foreign DNA introduced by calcium phosphate is integrated into repetitive DNA elements of the mouse L cell genome.

We investigated the sites of integration of exogenous DNA fragments introduced by DNA-mediated gene transfer. Mouse Ltk- cells were transformed with the herpes simplex virus thymidine kinase gene and pBR322 DNA by the calcium phosphate precipitation method. Some of the integrated exogenous DNA sequences were recovered from the stable tk+ transformants in the form of plasmids that were capable of propagation in bacteria. Four plasmids derived from two cloned cell lines were analyzed in detail by nucleotide sequencing and hybridization techniques. These plasmids contained a total of seven cellular-exogenous DNA junctions. In all cases, there was no sequence homology between the exogenous and cellular DNA sequences adjacent to the joining sites, and no specific exogenous or cellular sequences occurred at the junctions. Rearrangement or deletion of Ltk- DNA was always associated with the integration of exogenous DNA. All of the assignable cellular sequences at the junctions were repetitive sequences. Two of these sequences were from the MIF-1 repetitive sequence family, and a third consisted of a 40-base pair simple copolymer of alternating deoxyadenosine-deoxythymidine. Our results suggest that repetitive sequences are relatively favorable sites for the integration of exogenous DNA.     

Perspective: transposable elements, parasitic DNA, and genome evolution

The nature of the role played by mobile elements in host genome evolution is reassessed considering numerous recent developments in many areas of biology. It is argued that easy popular appellations such as "selfish DNA" and "junk DNA" may be either inaccurate or misleading and that a more enlightened view of the transposable element-host relationship encompasses a continuum from extreme parasitism to mutualism. Transposable elements are potent, broad spectrum, endogenous mutators that are subject to the influence of chance as well as selection at several levels of biological organization. Of particular interest are transposable element traits that early evolve neutrally at the host level but at a later stage of evolution are co-opted for new host functions.