Four Distances between Pairs of Amino Acids Provide a Precise Description of their Interaction

The three-dimensional structures of proteins are stabilized by the interactions between amino acid residues. Here we report a method where four distances are calculated between any two side chains to provide an exact spatial definition of their bonds. The data were binned into a four-dimensional grid and compared to a random model, from which the preference for specific four-distances was calculated. A clear relation between the quality of the experimental data and the tightness of the distance distribution was observed, with crystal structure data providing far tighter distance distributions than NMR data. Since the four-distance data have higher information content than classical bond descriptions, we were able to identify many unique inter-residue features not found previously in proteins. For example, we found that the side chains of Arg, Glu, Val and Leu are not symmetrical in respect to the interactions of their head groups. The described method may be developed into a function, which computationally models accurately protein structures

Developments in the remote sensing of soil erosion in the perspective of sub-Saharan Africa. Implications on future food security and biodiversity

The remote sensing of soil erosion has gained substantial consideration, with considerable scientific research work having been conducted in the past, due to technological improvements that have resulted in the release of robust, cheap and high resolution datasets with a global foot-print. This paper reviews developments in the application of remote sensing technologies in sub-Saharan Africa with a explicit emphasis on soil erosion monitoring. Soil loss due to soil erosion by water has been identified by African geomorphologists, environmentalists and governments, as the primary threat to agriculture, biodiversity and food security across the continent. The article offers a detailed review of the progress in the remote sensing as it summarises research work that have been conducted, using various remote sensing sensors and platforms and further evaluates the significance of variations in sensor resolutions and data availability for sub-Saharan Africa. Explicit application examples are used to highlight and outline this progress. Although some progress has been made, this review has revealed the necessity for further remote sensing work to provide time-series soil erosion modelling and its implications on future food security and biodiversity in the face of changing climate and food insecurity. Overall, this review have shown the immediate need for a drastical move towards the use of new generation sensors with a plausible spatial, temporal characteristics and more importantly a global foot-print

Protein structure modelling and evaluation based on a 4-distance description of side-chain interactions

<p>Abstract</p> <p>Background</p> <p>Accurate evaluation and modelling of residue-residue interactions within and between proteins is a key aspect of computational structure prediction including homology modelling, protein-protein docking, refinement of low-resolution structures, and computational protein design.</p> <p>Results</p> <p>Here we introduce a method for accurate protein structure modelling and evaluation based on a novel 4-distance description of residue-residue interaction geometry. Statistical 4-distance preferences were extracted from high-resolution protein structures and were used as a basis for a knowledge-based potential, called Hunter. We demonstrate that 4-distance description of side chain interactions can be used reliably to discriminate the native structure from a set of decoys. Hunter ranked the native structure as the top one in 217 out of 220 high-resolution decoy sets, in 25 out of 28 "<it>Decoys 'R' Us</it>" decoy sets and in 24 out of 27 high-resolution CASP7/8 decoy sets. The same concept was applied to side chain modelling in protein structures. On a set of very high-resolution protein structures the average RMSD was 1.47 Å for all residues and 0.73 Å for buried residues, which is in the range of attainable accuracy for a model. Finally, we show that Hunter performs as good or better than other top methods in homology modelling based on results from the CASP7 experiment. The supporting web site <url>http://bioinfo.weizmann.ac.il/hunter/</url> was developed to enable the use of Hunter and for visualization and interactive exploration of 4-distance distributions.</p> <p>Conclusions</p> <p>Our results suggest that Hunter can be used as a tool for evaluation and for accurate modelling of residue-residue interactions in protein structures. The same methodology is applicable to other areas involving high-resolution modelling of biomolecules.</p

Neopeptide Antibiotics That Function as Opsonins and Membrane-Permeabilizing Agents for Gram-Negative Bacteria

We suggest a novel approach to enhancing antimicrobial drug action by utilizing engineered peptide conjugates. Our most potent conjugates, [fMLF]PMBN and [fMLF]PMEN, are nonapeptides derived from polymyxin B's (PMB's) cyclic moiety (Thr-Dab-cyclo[Dab-Dab-d-Phe-Leu-Dab-Dab-Thr], where Dab is 2,4-diaminobutyric acid) and polymyxin E's (PME's) cyclic moiety (Thr-Dab-cyclo[Dab-Dab-d-Leu-Leu-Dab-Dab-Thr]), respectively, attached to a linear tail comprised of formyl-Met-Leu-Phe (fMLF). The cyclic part binds to gram-negative lipopolysaccharides, rendering the bacterial outer membrane permeable to hydrophobic antibiotics. The tail confers chemotactic and opsonic activities upon the conjugates. These two activities appear to be the basis for the conjugates' antibacterial activities. The conjugates are 8 to 10 times less toxic than the parent PMB or PME antibiotics. Fourteen of 18 mice lethally challenged with erythromycin-resistant Klebsiella pneumoniae survived following intraperitoneal administration of erythromycin and [fMLF]PMBN, whereas erythromycin or the peptide conjugate alone had no effect. Moreover, the clearance of Klebsiella from blood was markedly enhanced by intravenous injection of the [fMLF]PMEN peptide conjugate compared to the clearance of the organism from the mice treated with buffer alone as a control and was similar to that achieved by the PME antibiotic. Blood clearance was also significantly enhanced by administration of PMEN either alone or in a mixture with fMLF, although the effect was less than that produced by the peptide conjugate. Since resistance to polymyxins, the parent molecules of the synthetic cyclic peptides, is rare, the emergence of bacteria resistant to the antimicrobial properties of the peptide conjugates may be precluded as well