The representation of protein complexes in the Protein Ontology (PRO)

BACKGROUND: Representing species-specific proteins and protein complexes in ontologies that are both human- and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. DESCRIPTION: We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. CONCLUSION: PRO is a unique database resource for species-specific protein complexes. PRO facilitates robust annotation of variations in composition and function contexts for protein complexes within and between species

Pathway Projector: Web-Based Zoomable Pathway Browser Using KEGG Atlas and Google Maps API

BACKGROUND: Biochemical pathways provide an essential context for understanding comprehensive experimental data and the systematic workings of a cell. Therefore, the availability of online pathway browsers will facilitate post-genomic research, just as genome browsers have contributed to genomics. Many pathway maps have been provided online as part of public pathway databases. Most of these maps, however, function as the gateway interface to a specific database, and the comprehensiveness of their represented entities, data mapping capabilities, and user interfaces are not always sufficient for generic usage. METHODOLOGY/PRINCIPAL FINDINGS: We have identified five central requirements for a pathway browser: (1) availability of large integrated maps showing genes, enzymes, and metabolites; (2) comprehensive search features and data access; (3) data mapping for transcriptomic, proteomic, and metabolomic experiments, as well as the ability to edit and annotate pathway maps; (4) easy exchange of pathway data; and (5) intuitive user experience without the requirement for installation and regular maintenance. According to these requirements, we have evaluated existing pathway databases and tools and implemented a web-based pathway browser named Pathway Projector as a solution. CONCLUSIONS/SIGNIFICANCE: Pathway Projector provides integrated pathway maps that are based upon the KEGG Atlas, with the addition of nodes for genes and enzymes, and is implemented as a scalable, zoomable map utilizing the Google Maps API. Users can search pathway-related data using keywords, molecular weights, nucleotide sequences, and amino acid sequences, or as possible routes between compounds. In addition, experimental data from transcriptomic, proteomic, and metabolomic analyses can be readily mapped. Pathway Projector is freely available for academic users at (http://www.g-language.org/PathwayProjector/)

A DFT study of uracil and 5-bromouracil in nanodroplets

The canonical (keto) and rare (enol) tautomers of uracil and 5-bromouracil in clusters comprising 50 and 100 water molecules (nanodroplets) were studied using density functional theory. The geometries of the various complexes were optimized at two different levels of theory, BLYP/6-31G(d,p) and B3LYP/6-31G(d,p). Tautomerization energies were computed using the BLYP, B3LYP and M05-2X density functionals. The gas-phase tautomerization energies of uracil and 5-bromouracil are very similar, favoring the keto tautomer. However, in the hydrated phase, the tautomeric preference of 5-bromouracil is reversed. This result is obtained for all four sets of clusters (BLYP or B3LYP optimized, containing 50 or 100 water clusters) and at all levels of theory employed, and indicates that a bromine atom in the 5-position considerably increases the proportion of the hydroxyl group present in uracil.</p

Role of hydration in determining the structure and vibrational spectra of L-alanine and N-acetyl L-alanine N'-methylamide in aqueous solution: a combined theoretical and experimental approach

In this work we have utilised recent density functional theory Born-oppenheimer molecular dynamics simulations to determine the first principles locations of the water molecules in the first solvation shell which are responsible for stabilizing the zwitterionic structure of L-alanine. Previous works have used chemical intuition or classical molecular dynamics simulations to position the water molecules. In addition, a complete shell of water molecules was not previously used, only the water molecules which were thought to be strongly interacting (H-bonded) with the zwitterionic species. In a previous work by Tajkhorshid et al. (J Phys Chem B 102:5899) the l-alanine zwitterion was stabilized by 4 water molecules, and a subsequent work by Frimand et al. (Chem Phys 255:165) the number was increased to 9 water molecules. Here we found that 20 water molecules are necessary to fully encapsulate the zwitterionic species when the molecule is embedded within a droplet of water, while 11watermolecules are necessary to encapsulate the polar region with themethyl group exposed to the surface, where it migrates during the MD simulation. Here we present our vibrational absorption, vibrational circular dichroism and Raman and Raman optical activity simulations, which we compare to the previous simulations and experimental results. In addition, we report new VA, VCD, Raman and ROA measurements for l-alanine in aqueous solution with the latest commercially available FTIR VA/VCD instrument (Biotools, Jupiter, FL, USA) and Raman/ROA instrument (Biotools). The signal to noise of the spectra of l-alanine measured with these new instruments is significantly better than the previously reported spectra. Finally we reinvestigate the causes for the stability of the Pp structure of the alanine dipeptide, also called N-acetyl-l-alanine N-methylamide, in aqueous solution. Previously we utilized the B3LYP/6-31G* + Onsager continuum level of theory to investigate the stability of the ALANMA4WC Han et al. (J Phys Chem B 102:2587) Here we use the B3PW91 and B3LYP hybrid exchange correlation functionals, the aug-cc-pVDZ basis set and the PCMand CPCM (COSMO) continuum solvent models, in addition to the Onsager and no continuum solvent model. Here by the comparison of the VA, VCD, Raman and ROA spectra we can confirm the stability of the NALANMA4WC due to the strong hydrogen bonding between the fourwatermolecules and the peptide polar groups. Hence we advocate the use of explicit water molecules and continuum solvent treatment for all future spectral simulations of amino acids, peptides and proteins in aqueous solution, as even the structure (conformer) present cannot always be found without this level of theory