SwS: a solvation web service for nucleic acids

SwS, based on a statistical analysis of crystallographic structures deposited in the NDB, is designed to provide an exhaustive overview of the solvation of nucleic acid structural elements through the generation of 3D solvent density maps. A first version (v1.0) of this web service focuses on the interaction of DNA, RNA and hybrid base pairs linked by two or three hydrogen bonds with water, cations and/or anions. Data provided by SwS are updated on a weekly basis and can be used by: (i) those involved in molecular dynamics simulation studies for validation purposes; (ii) crystallographers for help in the interpretation of solvent density maps; and all those involved in (iii) drug design and, more generally, in (iv) nucleic acid structural studies. SwS provides also statistical data related to the frequency of occurrence of different types of base pairs in crystallographic structures and the conformation of the involved nucleotides. This web service has been designed to allow a maximum of flexibility in terms of queries and has also been developed with didactic considerations in mind. AVAILABILITY: http://www-ibmc.u-strasbg.fr/arn/sws.html     

Heat capacities of transfer of some amino acids and peptides from water to aqueous urea solution

Integral enthalpies of solution at low concentrations of several amino acids and peptides in 2 and 6M urea solutions have been determined at 25 and 35°C. These data have been used to derive the enthalpies of transfer (at 25 and 35°C) and heat capacities of transfer (at 30°C) of these amino acids and peptides from water to aqueous urea solutions. Furthermore, the enthalpies of transfer and heat capacities of transfer per CH₂ group and per peptide group ? CONH? have also been estimated. These results show that while the enthalpies and heat capacities of transfer per CH₂ group are positive and negative, respectively, the reverse is true for ? CONH? group. The implications of these results in the mechanism of the denaturation of proteins by urea are discussed.     

Gas chromatographic determination of free amino acids and amino acids attached to transfer RNA in biological samples

A method was developed to analyze quantitatively free amino acids and amino acids attached to transfer RNA (tRNA) in tissue samples by gas chromatography. Free amino acids were purified by ion-exchange chromatography after deproteinization. Total cellular aminoacyl-tRNA was extracted from rabbit reticulocytes and liver by a modified phenol extraction method under conditions which were designed to prevent deacylation of the attached amino acids. After deacylation and separation from tRNA by pressure ultrafiltration, eighteen amino acids were determined by gas chromatography as their N-heptafluorobutyryl isobutyl derivatives.     

Position-resolved free energy of solvation for amino acids in lipid membranes from molecular dynamics simulations

Studies of insertion and interactions of amino acids in lipid membranes are pivotal to our understanding of membrane protein structure and function. Calculating the insertion cost as a function of transmembrane helix sequence is thus an important step towards improved membrane protein prediction and eventually drug design. Here, we present position-dependent free energies of solvation for all amino acid analogs along the membrane normal. The profiles cover the entire region from bulk water to hydrophobic core, and were produced from all-atom molecular dynamics simulations. Experimental differences corresponding to mutations and costs for entire segments match experimental data well, and in addition the profiles provide the spatial resolution currently not available from experiments. Polar side-chains largely maintain their hydration and assume quite ordered conformations, which indicates the solvation cost is mainly entropic. The cost of solvating charged side-chains is not only significantly lower than for implicit solvation models, but also close to experiments, meaning these could well maintain their protonation states inside the membrane. The single notable exception to the experimental agreement is proline, which is quite expensive to introduce in vivo despite its hydrophobicity--a difference possibly explained by kinks making it harder to insert helices in the translocon.     

Thermodynamic parameters of transfer of N-acetyl ethyl esters of different amino acids from organic solvents to water.

The distribution coefficients of N-acetyl ethyl esters of glycine, diglycine, beta-alanine, alanine, valine, norvaline, leucine and norleucine between water and different organic solvents have been measured at different temperatures. Similar distribution coefficients have been measured for simple amides, urea, formamide, acetamide and N-methyl acetamide. From the distribution measurements, deltaGtr, the free energy of transfer of the solutes from organic solvents to water has been calculated. The temperature dependence of the distribution coefficient values has been utilised to determine the enthalpy of transfer, deltaHtr, and entropy of transfer deltaStr for the above process. From these results similar thermodynamic parameters for the transfer of different nonpolar side chains and peptide groups have been determined and compared with the available data in the literature.     

Splicing of unnatural amino acids into proteins: a peptide model study

S-Ethyl 2-azidohexanethioate (N3-Hex-SEt), an unnatural amino acid analog of leucine, is coupled with L-cysteine ethyl ester (NH2-Cys-OEt) to obtain N3-Hex-Cys-OEt by native chemical ligation. Coupling of this dipeptide with N-t-butoxycarbonyl-2-diphenylphosphinoethanethioglycinate produces the tripeptide, t-Boc-Gly-Hex-Cys-OEt, in high yield. These reactions suggest an approach for the incorporation of unnatural amino acids into proteins by successive native chemical ligation and Staudinger ligation.     

A model for the tertiary structure of transfer ribonucleic acids

In view of the possible changes of the structure of DNA at different relative humidities, a similar model for tRNA is proposed. In the native form, the sugar phosphate backbone folds repeatedly on itself resulting in a circular rod structure of about 50 Å in length and about 25 Å in diameter. Both the amino-acyl end and the anticodon site are surrounded by segments of base sequences common to different tRNA’s.     

A reexamination of the propensities of amino acids towards a particular secondary structure: classification of amino acids based on their chemical structure

The correlation between the primary and secondary structures of proteins was analysed using a large data set from the Protein Data Bank. Clear preferences of amino acids towards certain secondary structures classify amino acids into four groups: α-helix preferrers, strand preferrers, turn and bend preferrers, and His and Cys (the latter two amino acids show no clear preference for any secondary structure). Amino acids in the same group have similar structural characteristics at their Cβ and Cγ atoms that predicts their preference for a particular secondary structure. All α-helix preferrers have neither polar heteroatoms on Cβ and Cγ atoms, nor branching or aromatic group on the Cβ atom. All strand preferrers have aromatic groups or branching groups on the Cβ atom. All turn and bend preferrers have a polar heteroatom on the Cβ or Cγ atoms or do not have a Cβ atom at all. These new rules could be helpful in making predictions about non-natural amino acids.

Gating mechanism of mechanosensitive channel of large conductance: a coupled continuum mechanical-continuum solvation approach

Gating transition of the mechanosensitive channel of large conductance (MscL) represents a good example of important biological processes that are difficult to describe using atomistic simulations due to the large (submicron) length scale and long (millisecond) time scale. Here we develop a novel computational framework that tightly couples continuum mechanics with continuum solvation models to study the detailed gating behavior of E. coli-MscL. The components of protein molecules are modeled by continuum elements that properly describe their shape, material properties and physicochemical features (e.g., charge distribution). The lipid membrane is modeled as a three-layer material in which the lipid head group and tail regions are treated separately, taking into account the fact that fluidic lipid bilayers do not bear shear stress. Coupling between mechanical and chemical responses of the channel is realized by an iterative integration of continuum mechanics (CM) modeling and continuum solvation (CS) computation. Compared to previous continuum mechanics studies, the present model is capable of capturing the most essential features of the gating process in a much more realistic fashion: due mainly to the apolar solvation contribution, the membrane tension for full opening of MscL is reduced substantially to the experimental measured range. Moreover, the pore size stabilizes constantly during gating because of the intricate interactions of the multiple components of the system, implying the mechanism for sub-conducting states of MscL gating. A significant fraction (\(\sim \)2/3) of the gating membrane strain is required to reach the first sub-conducting state of our model, which is featured with a relative conductance of 0.115 to the fully opened state. These trends agree well with experimental observations. We anticipate that the coupled CM/CS modeling framework is uniquely suited for the analysis of many biomolecules and their assemblies under external mechanical stimuli.     

Acceleration of proton exchange between octanol and water by 2,4-dinitrophenol determined by 1H-NMR spectrometry a new model for proton transfer in a hydrophobic environment

The rate of proton transfer between the octanol -OH group and water dissolved in octanol after partition equilibrium was determined by ¹H-NMR spectrometry. The rate was found to depend on the pH of the aqueous phase, being minimal at about pH 11. The uncoupler of oxidative phosphorylation 2,4-dinitrophenol at about 10^?3 M accelerated proton transfer several-fold. Its effect was shown to depend on the concentration of the neutral form of 2,4-dinitrophenol in the octanol phase, irrespective of the pH of the aqueous phase. This effect is suggested to be based on the catalytic action of the phenolic -OH group in 2,4-dinitrophenol. The importance of this effect in the uncoupling action of 2,4-dinitrophenol is discussed.     

Receptor-level interrelationships of amino acids and the adequate amino acid type hormones in Tetrahymena: a receptor evolution model

Histidine stimulates the phagocytosis of Tetrahymena to the same extent as histamine, and also stimulates its division, which histamine does not. Tyrosine and diiodotyrosine equally stimulate the growth of the Tetrahymena. Both amino acids inhibit the characteristic influence of the adequate amino acid hormone when added to Tetrahymena culture 72 h in advance of it. Primary interaction with diiodotyrosine and tyrosine notably increases the cellular growth rate. Histamine has a similar, although less notable effect than histidine. In the light of these experimental observations there is reason to postulate that the receptors of the amino acid hormones have developed from amino acid receptors.     

In response to the continuum model for fauna research: a hierarchical, patch-based model of spatial landscape patterns

Models of nature are implicitly influenced by the scale of observation of the processes on which they are founded. The continuum model and the hierarchical patch-based model are two alternate approaches for the spatial modelling of fauna distribution. The continuum model aggregates continuous approximations to individual landscape characteristics, whereas the hierarchical patch-based model constructs a hierarchy in which classifications of landscape characteristics describe an interconnected series of patches. We propose the hierarchical patch-based theory for models of population distributions and landscapes in which the spatial patterns can be effectively represented by mosaics at the variety of levels within the set of individual process models. Given that observations are typically made as points or pixels, and that discrete boundaries exist in both natural and human-modified landscapes, we suggest that the hierarchical patch-based method has many applications in conservation and management.