Elastic properties of proteins: insight on the folding process and evolutionary selection of native structures

We carry out a theoretical study of the vibrational and relaxation properties of naturally-occurring proteins with the purpose of characterizing both the folding and equilibrium thermodynamics. By means of a suitable model we provide a full characterization of the spectrum and eigenmodes of vibration at various temperatures by merely exploiting the knowledge of the protein native structure. It is shown that the rate at which perturbations decay at the folding transition correlates well with experimental folding rates. This validation is carried out on a list of about 30 two-state folders. Furthermore, the qualitative analysis of residues mean square displacements (shown to accurately reproduce crystallographic data) provides a reliable and statistically accurate method to identify crucial folding sites/contacts. This novel strategy is validated against clinical data for HIV-1 Protease. Finally, we compare the spectra and eigenmodes of vibration of natural proteins against randomly-generated compact structures and regular random graphs. The comparison reveals a distinctive enhanced flexibility of natural structures accompanied by slow relaxation times at the folding temperature. The fact that these properties are intimately connected to the presence and assembly of secondary motifs hints at the special criteria adopted by evolution in the selection of viable folds.Comment: Revtex 17 pages, 13 eps figure

Optimized Data Representation for Interactive Multiview Navigation

In contrary to traditional media streaming services where a unique media content is delivered to different users, interactive multiview navigation applications enable users to choose their own viewpoints and freely navigate in a 3-D scene. The interactivity brings new challenges in addition to the classical rate-distortion trade-off, which considers only the compression performance and viewing quality. On the one hand, interactivity necessitates sufficient viewpoints for richer navigation; on the other hand, it requires to provide low bandwidth and delay costs for smooth navigation during view transitions. In this paper, we formally describe the novel trade-offs posed by the navigation interactivity and classical rate-distortion criterion. Based on an original formulation, we look for the optimal design of the data representation by introducing novel rate and distortion models and practical solving algorithms. Experiments show that the proposed data representation method outperforms the baseline solution by providing lower resource consumptions and higher visual quality in all navigation configurations, which certainly confirms the potential of the proposed data representation in practical interactive navigation systems

CATHEDRAL: A Fast and Effective Algorithm to Predict Folds and Domain Boundaries from Multidomain Protein Structures

We present CATHEDRAL, an iterative protocol for determining the location of previously observed protein folds in novel multidomain protein structures. CATHEDRAL builds on the features of a fast secondary-structure–based method (using graph theory) to locate known folds within a multidomain context and a residue-based, double-dynamic programming algorithm, which is used to align members of the target fold groups against the query protein structure to identify the closest relative and assign domain boundaries. To increase the fidelity of the assignments, a support vector machine is used to provide an optimal scoring scheme. Once a domain is verified, it is excised, and the search protocol is repeated in an iterative fashion until all recognisable domains have been identified. We have performed an initial benchmark of CATHEDRAL against other publicly available structure comparison methods using a consensus dataset of domains derived from the CATH and SCOP domain classifications. CATHEDRAL shows superior performance in fold recognition and alignment accuracy when compared with many equivalent methods. If a novel multidomain structure contains a known fold, CATHEDRAL will locate it in 90% of cases, with <1% false positives. For nearly 80% of assigned domains in a manually validated test set, the boundaries were correctly delineated within a tolerance of ten residues. For the remaining cases, previously classified domains were very remotely related to the query chain so that embellishments to the core of the fold caused significant differences in domain sizes and manual refinement of the boundaries was necessary. To put this performance in context, a well-established sequence method based on hidden Markov models was only able to detect 65% of domains, with 33% of the subsequent boundaries assigned within ten residues. Since, on average, 50% of newly determined protein structures contain more than one domain unit, and typically 90% or more of these domains are already classified in CATH, CATHEDRAL will considerably facilitate the automation of protein structure classification

Spike sorting for large, dense electrode arrays

Developments in microfabrication technology have enabled the production of neural electrode arrays with hundreds of closely spaced recording sites, and electrodes with thousands of sites are under development. These probes in principle allow the simultaneous recording of very large numbers of neurons. However, use of this technology requires the development of techniques for decoding the spike times of the recorded neurons from the raw data captured from the probes. Here we present a set of tools to solve this problem, implemented in a suite of practical, user-friendly, open-source software. We validate these methods on data from the cortex, hippocampus and thalamus of rat, mouse, macaque and marmoset, demonstrating error rates as low as 5%