Phase diagrams of lyotropic cholesteric fluids

Experimental investigations of lyotropic cholesterics fluids are presented which show that changes in the shape anisotropy and chirality of the micellar population determine the topology of the temperature-concentration phase diagrams. For given amounts of the substances which induce the chirality and modify the shape anisotropy of the micelles, two distinct biaxial cholesteric phases are disclosed in the phase diagrams. This is interpreted in the framework of the catastrophe theory of phase transitions.     

Protein structure prediction and biomolecular recognition: From protein sequence to peptidomimetic design with the human β 3 integrin

Computational tools can bridge the gap between sequence and protein 3D structure based on the notion that information is to be retrieved from the databases and that knowledge-based methods can help in approaching a solution of the protein-folding problem. To this aim our group has implemented neural network-based predictors capable of performing with some success in different tasks, including predictions of the secondary structure of globular and membrane proteins, the topology of membrane proteins and porins and stable f -helical segments suited for protein design. Moreover we have developed methods for predicting contact maps in proteins and the probability of finding a cysteine in a disulfide bridge, tools which can contribute to the goal of predicting the 3D structure starting from the sequence (the so called ab initio prediction). All our predictors take advantage of evolution information derived from the structural alignments of homologous (evolutionary related) proteins and taken from the sequence and structure databases. When it is necessary to build models for proteins of unknown spatial structure, which have very little homology with other proteins of known structure, non-standard techniques need to be developed and the tools for protein structure predictions may help in protein modeling. The results of a recent simulation performed in our lab highlights the role of high performing computing technology and of tools of computational biology in protein modeling and peptidomimetic design.     

Energy-based prediction of amino acid-nucleotide base recognition

Despite decades of investigations, it is not yet clear whether there are rules dictating the specificity of the interaction between amino acids and nucleotide bases. This issue was addressed by determining, in a dataset consisting of 100 high-resolution protein-DNA structures, the frequency and energy of interaction between each amino acid and base, and the energetics of water-mediated interactions. The analysis was carried out using HINT, a non-Newtonian force field encoding both enthalpic and entropic contributions, and Rank, a geometry-based tool for evaluating hydrogen bond interactions. A frequency- and energy-based preferential interaction of Arg and Lys with G, Asp and Glu with C, and Asn and Gln with A was found. Not only favorable, but also unfavorable contacts were found to be conserved. Water-mediated interactions strongly increase the probability of Thr-A, Lys-A, and Lys-C contacts. The frequency, interaction energy, and water enhancement factors associated with each amino acid-base pair were used to predict the base triplet recognized by the helix motif in 45 zinc fingers, which represents an ideal case study for the analysis of one-to-one amino acid-base pair contacts. The model correctly predicted 70.4% of 135 amino acid-base pairs, and, by weighting the energetic relevance of each amino acid-base pair to the overall recognition energy, it yielded a prediction rate of 89.7%.     

Working group report: Heavy-ion physics and quark-gluon plasma

This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09 which was part of Working Group-4. Discussion and work on some aspects of quark-gluon plasma believed to have created in heavy-ion collisions and in early Universe are reported.     

Simulation of conformational changes occurring when a protein interacts with its receptor

In order to simulate the conformational changes occurring when a protein interacts with its receptor, we firstly evaluated the structural differences between the experimental unbound and bound conformations for selected proteins and created theoretical complexes by replacing, in each experimental complex, the protein-bound with the protein-unbound chain. The theoretical models were then subjected to additional modeling refinements to improve the side chain geometry. Comparing the theoretical and experimental complexes in term of structural and energetic factors is resulted that the refined theoretical complexes became more similar to the experimental ones. We applied the same procedure within an homology modeling experiment, using as templates the experimental structures of human interleukin-1beta (IL-1beta) unbound and bound with its receptor, to build models of the homologous proteins from mouse and trout in unbound and bound conformations and to simulate the interaction with the related receptors. Our results suggest that homology modeling techniques are sensitive to differences between bound and unbound conformations, and that modeling with accuracy the side chains in the complex improves the interaction and molecular recognition. Moreover, our refinement procedure could be used in protein-protein interaction studies and, also, applied in conjunction with rigid-body docking when is not available the protein-bound conformation.     

PreSSAPro: a software for the prediction of secondary structure by amino acid properties

PreSSAPro is a software, available to the scientific community as a free web service designed to provide predictions of secondary structures starting from the amino acid sequence of a given protein. Predictions are based on our recently published work on the amino acid propensities for secondary structures in either large but not homogeneous protein data sets, as well as in smaller but homogeneous data sets corresponding to protein structural classes, i.e. all-alpha, all-beta, or alpha–beta proteins. Predictions result improved by the use of propensities evaluated for the right protein class. PreSSAPro predicts the secondary structure according to the right protein class, if known, or gives a multiple prediction with reference to the different structural classes. The comparison of these predictions represents a novel tool to evaluate what sequence regions can assume different secondary structures depending on the structural class assignment, in the perspective of identifying proteins able to fold in different conformations. The service is available at the URL http://bioinformatica.isa.cnr.it/PRESSAPRO/.     

Conformational diseases and structure-toxicity relationships: lessons from prion-derived peptides

The physiological form of the prion protein is normally expressed in mammalian cell and is highly conserved among species, although its role in cellular function remains elusive. Available evidence suggests that this protein is essential for neuronal integrity in the brain, possibly with a role in copper metabolism and cellular response to oxidative stress. In prion diseases, the benign cellular form of the protein is converted into an insoluble, protease-resistant abnormal scrapie form. This conversion parallels a conformational change of the polypeptide from a predominantly alpha-helical to a highly beta-sheet secondary structure. The scrapie form accumulates in the central nervous system of affected individuals, and its protease-resistant core aggregates into amyloid fibrils outside the cell. The pathogenesis and molecular basis of the nerve cell loss that accompanies this process are not understood. Limited structural information is available on aggregate formation by this protein as the possible cause of these diseases and on its toxicity. A large amount of structure-activity studies is based on the prion fragment approach, but the resulting information is often difficult to untangle. This overview focuses on the most relevant structural and functional aspects of the prion-induced conformational disease linked to peptides derived from the unstructured N-terminal and globular C-terminal domains.