Comparative studies of high-throughput biological graphs

Background The exponential growth of biological data has given rise to new and difficult challenges. Because large data is often dealt with, it is inefficient to infer from each individual characteristics of a given dataset. Bioinformaticists are developing quantitative techniques to analyze and interpret key data properties. Graph algorithms can provide powerful and intuitive insight on such properties [1]. Using this approach, we collect biological data from transcriptomic and protein-protein interaction (PPI) sources. These data can be represented as a correlation matrix, where the rows are the vertices and the columns are the edges. We will analyze these graphs, and describe their differing structural characteristics. Materials and methods We are using a high throughput method for graphical exploration of genomic and proteomic data. Experimental datasets are extracted from the public databases Biomart and Gene Expression Omnibus (GEO) [2,3]. R [4] and MATLAB are used to develop algorithms that compute and compare various structural characteristics. We specifically developed an in-house script used to output essential histograms and unweighted/weighted edges. We are currently developing protocols to analyze the comparison of transcriptomes and PPI sources. Acknowledgements We express gratitude towards Jay Snoddy and Michael Langston for the ideas that led us to pursue this bioinformatics investigation

Determining anion-quadrupole interactions among protein, DNA, and ligand molecules

Background An extensive search through the Protein Databank (about 4500 nonredundant structures) was previously completed within our lab to analyze the energetic and geometric characteristics of an understudied molecular interaction known as an anion-quadrupole (AQ) interaction. Such an interaction occurs when the positively charged edge of an aromatic ring, resulting from a quadruple moment (i.e., a dual dipole moment), renders the aromatic molecule noncovalently bound to a nearby anionic molecule. The study considered a very limited scenario of molecules that can participate in AQ interactions, consisting of the phenyl group of a phenylalanine (phe) amino acid as the aromatic participant and the carboxylate group of an aspartate (asp) or glutamate (glu) amino acid as the anionic participant. The results revealed anion-quadrupole pairs to be prevalent within most of the protein structures. It was also observed that the interaction energy for AQ pairs was heavily dependent on the angle between the anion and plane of the aromatic ring, favoring a more planar interaction. In light of these critical observations being made from such a limited scenario, only phe-glu and phe-asp pairs and in a reduced sample set of the PDB, we are now continuing this work of identifying AQ interactions using a greatly expanded strategy. We are following these four aims: 1. Optimizing the AQ-search program to run in a semi-parallel fashion and on a large cluster of processors in order to handle larger analyses, 2. Adding to our search additional anionic participants which will include non-protein structures such as DNA and small ligands, 3. Studying a subset of the AQ pairs with molecular dynamics simulations in buried and solvent exposed environments to observe non-static behavioral traits as well as the reproducibility of AQ interactions by force field parameters. 4. Building an online database for public access to our data and search program. Acknowledgments We would like to acknowledge the NSF-IGERT traineeship, Scalable Computing and Leading Edge Innovative Technologies (SCALE-IT), for providing the resources for this project

Oxpholipin 11D: An Anti-Inflammatory Peptide That Binds Cholesterol and Oxidized Phospholipids

Background: Many Gram-positive bacteria produce pore-forming exotoxins that contain a highly conserved, 12-residue domain (ECTGLAWEWWRT) that binds cholesterol. This domain is usually flanked N-terminally by arginine and C-terminally by valine. We used this 14-residue sequence as a template to create a small library of peptides that bind cholesterol and other lipids. Methodology/Results: Several of these peptides manifested anti-inflammatory properties in a predictive in vitro monocyte chemotactic assay, and some also diminished the pro-inflammatory effects of low-density lipoprotein in apoE-deficient mice. The most potent analog, Oxpholipin-11D (OxP-11D), contained D-amino acids exclusively and was identical to the 14residue design template except that diphenylalanine replaced cysteine-3. In surface plasmon resonance binding studies, OxP-11D bound oxidized (phospho)lipids and sterols in much the same manner as D-4F, a widely studied cardioprotective apoA-I-mimetic peptide with anti-inflammatory properties. In contrast to D-4F, which adopts a stable a-helical structure in solution, the OxP-11D structure was flexible and contained multiple turn-like features. Conclusion: Given the substantial evidence that oxidized phospholipids are pro-inflammatory in vivo, OxP-11D and othe

Oxpholipin 11D: an anti-inflammatory peptide that binds cholesterol and oxidized phospholipids.

BackgroundMany gram-positive bacteria produce pore-forming exotoxins that contain a highly conserved, 12-residue domain (ECTGLAWEWWRT) that binds cholesterol. This domain is usually flanked N-terminally by arginine and C-terminally by valine. We used this 14-residue sequence as a template to create a small library of peptides that bind cholesterol and other lipids.Methodology/resultsSeveral of these peptides manifested anti-inflammatory properties in a predictive in vitro monocyte chemotactic assay, and some also diminished the pro-inflammatory effects of low-density lipoprotein in apoE-deficient mice. The most potent analog, Oxpholipin-11D (OxP-11D), contained D-amino acids exclusively and was identical to the 14-residue design template except that diphenylalanine replaced cysteine-3. In surface plasmon resonance binding studies, OxP-11D bound oxidized (phospho)lipids and sterols in much the same manner as D-4F, a widely studied cardioprotective apoA-I-mimetic peptide with anti-inflammatory properties. In contrast to D-4F, which adopts a stable alpha-helical structure in solution, the OxP-11D structure was flexible and contained multiple turn-like features.ConclusionGiven the substantial evidence that oxidized phospholipids are pro-inflammatory in vivo, OxP-11D and other Oxpholipins may have therapeutic potential