Computational vaccinology: quantitative approaches.

The immune system is hierarchical and has many levels, exhibiting much emergent behaviour. However, at its heart are molecular recognition events that are indistinguishable from other types of biomacromolecular interaction. These can be addressed well by quantitative experimental and theoretical biophysical techniques, and particularly by methods from drug design. We review here our approach to computational immunovaccinology. In particular, we describe the JenPep database and two new techniques for T cell epitope prediction. One is based on quantitative structure-activity relationships (a 3D-QSAR method based on CoMSIA and another 2D method based on the Free-Wilson approach) and the other on atomistic molecular dynamic simulations using high performance computing. JenPep (http://www.jenner.ar.uk/ JenPep) is a relational database system supporting quantitative data on peptide binding to major histocompatibility complexes, TAP transporters, TCR-pMHC complexes, and an annotated list of B cell and T cell epitopes. Our 2D-QSAR method factors the contribution to peptide binding from individual amino acids as well as 1-2 and 1-3 residue interactions. In the 3D-QSAR approach, the influence of five physicochemical properties (volume, electrostatic potential, hydrophobicity, hydrogen-bond donor and acceptor abilities) on peptide affinity were considered. Both methods are exemplified through their application to the well-studied problem of peptide binding to the human class I MHC molecule HLA-A*0201

Sulfonated Graphene Oxide Platelets in Nafion Nanocomposite Membrane: Advantages for Application in Direct Methanol Fuel Cells

Graphene oxide (GO) is well known as an excellent amphiphilic material due to its oxygen-containing functional groups and its chemical tunability. By intercalation chemistry, organo-modified GO containing sulfonilic terminal groups were prepared and used as nanoadditive in Nafion polymer for the creation of hybrid exfoliated composites. The incorporation of hydrophilic 2D platelike layers in the Nafion membranes is expected to induce advantages in terms of thermal stability and mechanical and barrier properties (limitation of the methanol crossover by increased tortuosity and obstruction effect), although it may negatively affect the proton conductivity. In this work, we show how different preparation methods of the nanocomposites influence morphology, transport properties, and barrier effect to methanol. The hybrid membranes are characterized by powder X-ray diffraction and microscopies (SEM, TEM, and AFM). Water and methanol transport properties inside the nanocomposites are investigated by NMR spectroscopy (diffusivity and relaxation times), unveiling a reduction of the methanol diffusion and, nevertheless, an increase in the proton mobility and water retention at high temperatures. Finally, the electrochemical properties are investigated by direct methanol fuel cell (DMFC) tests, showing a significant reduction of the ohmic losses at high temperatures, extending in this way the operating range of a DMFC

Sulfonated graphene oxide platelets in nafion nanocomposite membrane: Advantages for application in direct methanol fuel cells

Graphene oxide (GO) is well known as an excellent amphiphilic material due to its oxygen-containing functional groups and its chemical tunability. By intercalation chemistry, organo-modified GO containing sulfonilic terminal groups were prepared and used as nanoadditive in Nafion polymer for the creation of hybrid exfoliated composites. The incorporation of hydrophilic 2D platelike layers in the Nafion membranes is expected to induce advantages in terms of thermal stability and mechanical and barrier properties (limitation of the methanol crossover by increased tortuosity and obstruction effect), although it may negatively affect the proton conductivity. In this work, we show how different preparation methods of the nanocomposites influence morphology, transport properties, and barrier effect to methanol. The hybrid membranes are characterized by powder X-ray diffraction and microscopies (SEM, TEM, and AFM). Water and methanol transport properties inside the nanocomposites are investigated by NMR spectroscopy (diffusivity and relaxation times), unveiling a reduction of the methanol diffusion and, nevertheless, an increase in the proton mobility and water retention at high temperatures. Finally, the electrochemical properties are investigated by direct methanol fuel cell (DMFC) tests, showing a significant reduction of the ohmic losses at high temperatures, extending in this way the operating range of a DMFC

Oxidized-Multiwalled Carbon Nanotubes as Non-Toxic Nanocarriers for Hydroxytyrosol Delivery in Cells

Carbon nanotubes (CNTs) possess excellent physicochemical and structural properties alongside their nano dimensions, constituting a medical platform for the delivery of different therapeutic molecules and drug systems. Hydroxytyrosol (HT) is a molecule with potent antioxidant properties that, however, is rapidly metabolized in the organism. HT immobilized on functionalized CNTs could improve its oral absorption and protect it against rapid degradation and elimination. This study investigated the effects of cellular oxidized multiwall carbon nanotubes (oxMWCNTs) as biocompatible carriers of HT. The oxidation of MWCNTs via H2SO4 and HNO3 has a double effect since it leads to increased hydrophilicity, while the introduced oxygen functionalities can contribute to the delivery of the drug. The in vitro effects of HT, oxMWCNTS, and oxMWCNTS functionalized with HT (oxMWCNTS_HT) were studied against two different cell lines (NIH/3T3 and Tg/Tg). We evaluated the toxicity (MTT and clonogenic assay), cell cycle arrest, and reactive oxygen species (ROS) formation. Both cell lines coped with oxMWCNTs even at high doses. oxMWCNTS_HT acted as pro-oxidants in Tg/Tg cells and as antioxidants in NIH/3T3 cells. These findings suggest that oxMWCNTs could evolve into a promising nanocarrier suitable for targeted drug delivery in the future

PRINTS and its automatic supplement, prePRINTS

The PRINTS database houses a collection of protein fingerprints. These may be used to assign uncharacterised sequences to known families and hence to infer tentative functions. The September 2002 release (version 36.0) includes 1800 fingerprints, encoding ∼11 000 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. In addition to its continued steady growth, we report here the development of an automatic supplement, prePRINTS, designed to increase the coverage of the resource and reduce some of the manual burdens inherent in its maintenance. The databases are accessible for interrogation and searching at http://www.bioinf.man.ac.uk/dbbrowser/PRINTS/

Sulfonated Graphene Oxide Platelets in Nafion Nanocomposite Membrane: Advantages for Application in Direct Methanol Fuel Cells

Graphene oxide (GO) is well known as an excellent amphiphilic material due to its oxygen-containing functional groups and its chemical tunability. By intercalation chemistry, organo-modified GO containing sulfonilic terminal groups were prepared and used as nanoadditive in Nafion polymer for the creation of hybrid exfoliated composites. The incorporation of hydrophilic 2D platelike layers in the Nafion membranes is expected to induce advantages in terms of thermal stability and mechanical and barrier properties (limitation of the methanol crossover by increased tortuosity and obstruction effect), although it may negatively affect the proton conductivity. In this work, we show how different preparation methods of the nanocomposites influence morphology, transport properties, and barrier effect to methanol. The hybrid membranes are characterized by powder X-ray diffraction and microscopies (SEM, TEM, and AFM). Water and methanol transport properties inside the nanocomposites are investigated by NMR spectroscopy (diffusivity and relaxation times), unveiling a reduction of the methanol diffusion and, nevertheless, an increase in the proton mobility and water retention at high temperatures. Finally, the electrochemical properties are investigated by direct methanol fuel cell (DMFC) tests, showing a significant reduction of the ohmic losses at high temperatures, extending in this way the operating range of a DMFC