Rigorous conformational analysis of right and left DNA helices and junction between them

On the basis of complete scanning through conformational space of dihedral angles, twelve structural genera were obtained. Subsequent energy minimization within these genera yielded a limited set of duplexes with stacking: right-handed B-form (Wilkins type), B2-form (Watson and Crick type) and left-handed Ll-form (Sasisekharan type) and the new L2-form. In the polymeric DNA only right-handed double-helices are possible, the left-handed helices are forbidden due to poor 1–5 interchain contacts. In contrast, for short fragments the left- and right-handed helicek have practically the same energies providing some physical ground for side-by-side form, which biologically is possible as recombination form and may be as replication form.     

Structure of the hydration shells of oligo(dA-dT).oligo(dA-dT) and oligo(dA).oligo(dT) tracts in B-type conformation on the basis of Monte Carlo calculations

Monte Carlo simulations [(N, V, T)-ensemble] were performed for the hydration shell of poly(dA-dT).poly(dA-dT) in canonical B form and for the hydration shell of poly(dA).poly(dT) in canonical B conformation and in a conformation with narrow minor groove, highly inclined bases, but with a nearly zero-inclined base pair plane (B' conformation). We introduced helical periodic boundary conditions with a rather small unit cell and a limited number of water molecules to reduce the dimensionality of the configuration space. The coordinates of local maxima of water density and the properties of one- and two-membered water bridges between polar groups of the DNA were obtained. The AT-alternating duplex hydration mirrors the dyad symmetry of polar group distribution. At the dApdT step, a water bridge between the two carbonyl oxygens O2 of thymines is formed as in the central base-pair step of Dickerson's dodecamer. In the major groove, 5-membered water chains along the tetranucleotide pattern d(TATA).d(TATA) are observed. The hydration geometry of poly(dA).poly(dT) in canonical B conformation is distinguished by autonomous primary hydration of the base-pair edges in both grooves. When this polymer adopts a conformation with highly inclined bases and narrow minor groove, the water density distribution in the minor groove is in excellent agreement with Dickerson's spine model. One local maximum per base pair of the first layer is located near the dyad axis between adjacent base pairs, and one local maximum per base pair in the second shell lies near the dyad axis of the base pair itself. The water bridge between the two strands formed within the first layer was observed with high probability. But the water molecules of the second layer do not have a statistically favored orientation necessary for bridging first layer waters. In the major groove, the hydration geometry of the (A.T) base-pair edge resembles the main features of the AT-pair hydration derived from other sequences for the canonical B form. The preference of the B' conformation for oligo(dA).oligo(dT) tracts may express the tendency to common hydration of base-pair edges of successive base pairs in the grooves of B-type DNA. The mean potential energy of hydration of canonical B-DNA was estimated to be -60 to -80 kJ/mole nucleotides in dependence on the (G.C) contents. Because of the small system size, this estimation is preliminary.     

A code controlling specific binding of regulatory proteins to DNA

A possible code is suggested that describes a correspondence between amino acid sequences in stereospecific sites of regulatory proteins and nucleotide sequences at the control sites on DNA. Stereospecific sites of regulatory proteins are assumed to contain pairs of antiparallel polypeptide chain segments which form a right-hand twisted antiparallel -sheet with single-stranded regions at the ends of the -structure. The binding reaction between regulatory protein and double-helical DNA is accompanied by significant structural alterations at stereospecific sites of the protein and DNA. Half of the hydrogen bonds normally existing in -structure are broken upon complex formation with DNA and a new set of hydrogen bonds is formed between polypeptide amide groups and DNA base pairs. The code states a correspondence between four amino acid residues at a stereospecific site of the regulatory protein and an AT (GC) base pair at the control site. It predicts that there are six fundamental amino acid residues (serine, threonine, histidine, asparagine, glutamine and cysteine) whose arrangement in the stereospecific site determines the base pair sequence to which a given regulatory protein would bind preferentially.     

Long-distance interactions and principles of molecular recognition at various biosystem organization levels

Efficient molecular recognition, in which recognition processes are occurring much faster than it takes to test variants, is only possible when long-distance recognition occurs together with contact interactions. The distance between interacting molecules should be sufficiently long to prevent hindrances to the search and, on the other hand, sufficiently short to provide selectivity. It was demonstrated that both of these two requirements can be satisfied simultaneously for biological macromolecules that include helical segments. Because the “diameters” of helical molecules are far shorter than their lengths, the intermolecular distance can be far greater than the diameters, thus allowing a free search. The distance can be far shorter than the lengths at the same time, thus providing selectivity. Analytical procedures were developed to estimate the parameters for protein–protein and protein–nucleic acid recognition. The coincidence of the charge-distribution periods in helical segments was found to substantially increase their interaction potential, and the reduction scale characteristic of the potential was shown to depend on the numerical value of the coinciding period.     

Two-H-bonded and one-H-bonded structure alternations in collagen

This paper concerns the conformational variability of collagen as related to the concrete tripeptides (GXY)n constituting its primary structure. The previously elaborated model (V.G.Tumanyan, N.G.Esipova, Biophysics 28, 1021-1025, 1983) with two nets of hydrogen bonds is useful for tripeptides where X is an amino acid. If X is an imino acid, the common one-bonded Rich & Crick model is valid. In this work, compound sequences including tripeptides of different types are considered. Molecular mechanics is used to assess the conformations of the junction regions when a structure with two nets of hydrogen bonds precedes the structure with one net, and vice versa. Thus, all types of sequences typical for natural collagen are covered. It is shown that the combined model representing an alternation of the two-H-bonded model and the one-H-bonded Rich & Crick model is satisfactory stereochemically, and provides more favorable energy in comparison with the continuous one-H-bonded model. Besides, a more favorable hydration of the molecule occures in this case. Some conclusions are made about interchain and intrachain ionic bonds. Thus, it is deduced for the concrete fibrillar protein how a one-dimensional structure determines three-dimensional structure. The macromolecular structure thus suggested is in accord with the experimental data on hydrogen exchange.     

Voluntary Attention and Quality of Life in Patients With Type 1 and Type 2 Diabetes Mellitus: Differences in Changes Depending on Disease Type and Duration

Journal of Evolutionary Biochemistry and Physiology - This article covers the study of cognitive processes in patients with type 1 and type 2 diabetes mellitus (DM) with disease duration of...     

DNA sequencing using specific long-range interaction between macromolecules

On the basis of the theory of specific long-range interaction between long molecules, an approach has been elaborated for «fast reading» of nucleotide sequences in one DNA molecule. First, a stretching force is applied to the molecule that causes its unwinding from B-form to S-form. Then, the molecule is placed in the stretched state on a support. After this, the electrostatic potential is estimated in a space along the DNA filament. The information obtained is sufficient for deducing the nucleotide sequence. Another approach to the «reading» of information reduces to measurement of the deformation of filament elements induced by the electric field from the electrode that stretches the filament by an alternating current applied.     

Periodicities in nucleotide distribution in the immunoglobulin light chain locus of Gallus gallus

Fourier spectra of nucleotide sequences from chicken (Gallus gallus) chromosome 15 were obtained. Periodical structures of several fragments of the Ig light chain locus were characterized. The Fourier spectra of the locus and its parts (variable and constant segments, enhancer, and sequences supposedly associated with somatic hypermutation) were shown to be unique among those of other chromosome 15 fragments.     

Potential-Energy surface for double-helical DNA with Watson-Crick Pairs. I. Complete scanning in the space of torsion angles

Complete scanning of correct double-helical DNA structures was performed in the space of torsion angles using rapid analytical procedures for generation of regular double helices with Watson-Crick base pairs. Potential energy of structures was calculated by pair-wise potential functions and used as necessary condition to single out physically meaningful forms. We found 12 discrete potential wells containing these physically meaningful forms, with only one well containing all classical forms (A, B, etc.). On the basis of the new structures listed, alternative models for DNA and DNA-like polymers and appropriate conformations for fluctuations leading to DNA bending and kink formation are suggested.     

Descriptive statistics of disallowed regions and various protein secondary structures in the context of studying twisted β-hairpins

A detailed analysis of polypeptide-chain backbone conformations was carried out for polypeptide-chain segments adjacent to β-turn regions, including the sites of disallowed conformations. A cross comparison of conformations was performed for disallowed regions of the Ramachandran plot and main types of β-turns and adjacent secondary structures. Based on the results, disallowed region 2 (II, II') in the Ramachandran plot was shown to coincide mainly with β-hairpins and, more exactly, twisted β-hairpins. The frequency of residues with angles ?_i, ψ_i that fall in region 2 (II, II') in the latter is 140 times higher than in common β-hairpins.