RESUMO

Motivation: Chemical shifts (CS) are an important source of structural information of macromolecules such as RNA. In addition to the scarce availability of CS for RNA, the observed values are prone to errors due to a wrong re-calibration or miss assignments. Different groups have dedicated their efforts to correct CS systematic errors on RNA. Despite this, there are not automated and freely available algorithms for evaluating the referencing of RNA 13 C CS before their deposition to the BMRB or re-reference already deposited CS with systematic errors. Results: Based on an existent method we have implemented an open source python module to correct 13 C CS (from here on 13Cexp) systematic errors of RNAs and then return the results in 3 formats including the nmrstar one. Availability and implementation: This software is available on GitHub at https://github.com/BIOS-IMASL/13Check_RNA under a MIT license. Supplementary information: Supplementary data are available at Bioinformatics online.

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There is a need to develop widely applicable tools to understand glycan organization, diversity and structure. We present a graph-theoretical study of a large sample of glycans in terms of finite dimension, a new metric which is an adaptation to finite sets of the classical Hausdorff "fractal" dimension. Every glycan in the sample is encoded, via finite dimension, as a point of Glycan Space, a new notion introduced in this paper. Two major outcomes were found: (a) the existence of universal bounds that restrict the universe of possible glycans and show, for instance, that the graphs of glycans are a very special type of chemical graph, and (b) how Glycan Space is related to biological domains associated to the analysed glycans. In addition, we discuss briefly how this encoding may help to improve search in glycan databases.

RESUMO

To account for the relative contributions of lysine and alanine residues to the stability of alpha-helices of copolymers of these two residues, conformational energy calculations were carried out for several hexadecapeptides at several pHs. All the calculations considered explicitly the coupling between the conformation of the molecule and the ionization equilibria as a function of pH. The total free energy function used in these calculations included terms that account for the solvation free energy and free energy of ionization. These terms were evaluated by means of a fast multigrid boundary element method. Reasonable agreement with experimental values was obtained for the helix contents and vicinal coupling constants ((3)J(HNalpha)). The helix contents were found to depend strongly on the lysine content, in agreement with recent experimental results of Williams et al. (Journal of the American Chemical Society, 1998, Vol. 120, pp. 11033-11043) In the lowest energy conformation computed for a hexadecapeptide containing 3 lysine residues at pH 6, the lysine side chains are preferentially hydrated; this decreases the hydration of the backbone CO and NH groups, thereby forcing the latter to form hydrogen bonds with each other in the helical conformation. The lowest energy conformation computed for a hexadecapeptide containing 6 lysine residues at pH 6 shows a close proximity between the NH3(+) groups of the lysine side chains, a feature that was previously observed in calculations of short alanine-based oligopeptides. The calculation on a blocked 16-mer of alanine shows a 7% helix content based on the Boltzmann averaged vicinal coupling constants computed from the dihedral angles phi, consistent with previous experimental evidence on triblock copolymers containing a central block of alanines, and with earlier theoretical calculations.

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We have carried out conformational energy calculations on alanine-based copolymers with the sequence Ac-AAAAAXAAAA-NH(2) in water, where X stands for lysine or glutamine, to identify the underlying source of stability of alanine-based polypeptides containing charged or highly soluble polar residues in the absence of charge-charge interactions. The results indicate that ionizable or neutral polar residues introduced into the sequence to make them soluble sequester the water away from the CO and NH groups of the backbone, thereby enabling them to form internal hydrogen bonds. This solvation effect dictates the conformational preference and, hence, modifies the conformational propensity of alanine residues. Even though we carried out simulations for specific amino acid sequences, our results provide an understanding of some of the basic principles that govern the process of folding of these short sequences independently of the kind of residues introduced to make them soluble. In addition, we have investigated through simulations the effect of the bulk dielectric constant on the conformational preferences of these peptides. Extensive conformational Monte Carlo searches on terminally blocked 10-mer and 16-mer homopolymers of alanine in the absence of salt were carried out assuming values for the dielectric constant of the solvent epsilon of 80, 40, and 2. Our simulations show a clear tendency of these oligopeptides to augment the alpha-helix content as the bulk dielectric constant of the solvent is lowered. This behavior is due mainly to a loss of exposure of the CO and NH groups to the aqueous solvent. Experimental evidence indicates that the helical propensity of the amino acids in water shows a dramatic increase on addition of certain alcohols, such us trifluoroethanol. Our results provide a possible explanation of the mechanism by which alcohol/water mixtures affect the free energy of helical alanine oligopeptides relative to nonhelical ones.

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A theoretical study to identify the conformational preferences of lysine-based oligopeptides has been carried out. The solvation free energy and free energy of ionization of the oligopeptides have been calculated by using a fast multigrid boundary element method that considers the coupling between the conformation of the molecule and the ionization equilibria explicitly, at a given pH value. It has been found experimentally that isolated alanine and lysine residues have somewhat small intrinsic helix-forming tendencies; however, results from these simulations indicate that conformations containing right-handed alpha-helical turns are energetically favorable at low values of pH for lysine-based oligopeptides. Also, unusual patterns of interactions among lysine side chains with large hydrophobic contacts and close proximity (5-6 A) between charged NH3+ groups are observed. Similar arrangements of charged groups have been seen for lysine and arginine residues in experimentally determined structures of proteins available from the Protein Data Bank. The lowest-free-energy conformation of the sequence Ac-(LYS)6-NMe from these simulations showed large pKalpha shifts for some of the NH3+ groups of the lysine residues. Such large effects are not observed in the lowest-energy conformations of oligopeptide sequences with two, three, or four lysine residues. Calculations on the sequence Ac-LYS-(ALA)4-LYS-NMe also reveal low-energy alpha-helical conformations with interactions of one of the LYS side chains with the helix backbone in an arrangement quite similar to the one described recently by (Proc. Natl. Acad. Sci. U.S.A. 93:4025-4029). The results of this study provide a sound basis with which to discuss the nature of the interactions, such as hydrophobicity, charge-charge interaction, and solvent polarization effects, that stabilize right-handed alpha-helical conformations.

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