Structural and thermodynamic analysis of heteroassociation of daunomycin and flavin mononucleotide molecules in water by <Superscript>1</Superscript>H NMR spectroscopy

Heteroassociation of the antitumor antibiotic daunomycin (DAU) with flavin mononucleotide (FMN) has been investigated by one-and two-dimensional ¹H NMR spectroscopy (500 MHz) in a water solution to determine the molecular mechanism of the combined action of the antibiotic and vitamin in the FMN-DAU system. The equilibrium constants of the reactions, induced proton chemical shifts, and thermodynamic parameters (ΔH, ΔS) of heteroassociation were determined from the concentration and temperature dependences of the proton chemical shifts in the interacting aromatic molecules. Analysis of the results indicate that heterocomplexes of riboflavin mononucleotide and daunomycin are formed due to stacking interactions between aromatic chromophores. The most probable spatial structure of the 1:1 DAU-FMN heterocomplex was determined by the molecular dynamics method using the X-PLOR program and the results of the analysis of the induced proton chemical shifts in molecules. Calculation of the relative content of self-and hetero-complexes of daunomycin for different values of the ratio (r) between the concentrations of flavin mononucleotide and daunomycin demonstrated that for r > 3, the contribution of DAU-FMN heterocomplexes to the equilibrium distribution of associates in aqueous solution is dominant. It is concluded that the aromatic molecules of vitamins, in particular, riboflavin, can form energetically strong heteroassociates with antitumor antibiotics in water solution and can thereby affect their medical and biological activity.     

Thermodynamics of binding of D-galactose and deoxy derivatives thereof to the L-arabinose-binding protein

We report the thermodynamics of binding of d-galactose and deoxy derivatives thereof to the arabinose binding protein (ABP). The "intrinsic" (solute-solute) free energy of binding DeltaG degrees (int) at 308 K for the 1-, 2-, 3-, and 6-hydroxyl groups of galactose is remarkably constant (approximately -30 kJ/mol), despite the fact that each hydroxyl group subtends different numbers of hydrogen bonds in the complex. The substantially unfavorable enthalpy of binding (approximately 30 kJ/mol) of 1-deoxygalactose, 2-deoxygalactose, and 3-deoxygalactose in comparison with galactose, cannot be readily accounted for by differences in solvation, suggesting that solute-solute hydrogen bonds are enthalpically significantly more favorable than solute-solvent hydrogen bonds. In contrast, the substantially higher affinity for 2-deoxygalactose in comparison with either 1-deoxygalactose or 3-deoxygalactose derives from differences in the solvation free energies of the free ligands.     

MoDEL: an efficient strategy for ungapped local multiple alignment

We introduce a method for ungapped local multiple alignment (ULMA) in a given set of amino acid or nucleotide sequences. This method explores two search spaces using a linked optimization strategy. The first search space M consists of all possible words of a given length W, defined on the residue alphabet. An evolutionary algorithm searches this space globally. The second search space P consists of all possible ULMAs in the sequence set, each ULMA being represented by a position vector defining exactly one subsequence of length W per sequence. This search space is sampled with hill-climbing processes. The search of both spaces are coupled by projecting high scoring results from the global evolutionary search of M onto P. The hill-climbing processes then refine the optimization by local search, using the relative entropy between the ULMA and background residue frequencies as an objective function. We demonstrate some advantages of our strategy by analyzing difficult natural amino acid sequences and artificial datasets. A web interface is available at     

Update on nuclear structure effects in light muonic atoms

We present calculations of the nuclear structure corrections to the Lamb shift in light muonic atoms, using state-of-the-art nuclear potentials. We outline updated results on finite nucleon size contributions.     

Balleans of topological groups

A subset S of a topological group G is called bounded if, for every neighborhood U of the identity of G, there exists a finite subset F such that S ⊆ FU, S ⊆ UF. The family of all bounded subsets of G determines two structures on G, namely the left and right balleans B _l (G) and B _r (G), which are counterparts of the left and right uniformities of G. We study the relationships between the uniform and ballean structures on G, describe all topological groups admitting a metric compatible both with uniform and ballean structures, and construct a group analogue of Higson’s compactification of a proper metric space.