Aligning sequences to structures

Most newly sequenced proteins are likely to adopt a similar structure to one which has already been experimentally determined. For this reason, the most successful approaches to protein structure prediction have been template-based methods. Such prediction methods attempt to identify and model the folds of unknown structures by aligning the target sequences to a set of representative template structures within a fold library. In this chapter, I discuss the development of template-based approaches to fold prediction, from the traditional techniques to the recent state-of-the-art methods. I also discuss the recent development of structural annotation databases, which contain models built by aligning the sequences from entire proteomes against known structures. Finally, I run through a practical step-by-step guide for aligning target sequences to known structures and contemplate the future direction of template-based structure prediction.

A test of the master gene hypothesis for interspersed repetitive DNA sequences

Many families of interspersed repetitive DNA elements, including human Alu and LINE (Long Interspersed Element) elements, have been proposed to have accumulated through repeated copying from a single source locus: the "master gene." The extent to which a master gene model is applicable has implications for the origin, evolution, and function of such sequences. One repetitive element family for which a convincing case for a master gene has been made is the rodent ID (identifier) elements. Here we devise a new test of the master gene model and use it to show that mouse ID element sequences are not compatible with a strict master gene model. We suggest that a single master gene is rarely, if ever, likely to be responsible for the accumulation of any repeat family.

Phylogeny of Pelargonium (Geraniaceae) based on DNA sequences from three genomes

Phylogenetic hypotheses for the largely South African genus Pelargonium L'Hér. (Geraniaceae) were derived based on DNA sequence data from nuclear, chloroplast and mitochondrial encoded regions. The datasets were unequally represented and comprised cpDNA trnL-F sequences for 152 taxa, nrDNA ITS sequences for 55 taxa, and mtDNA nad1 b/c exons for 51 taxa. Phylogenetic hypotheses derived from the separate three datasets were overall congruent. A single hypothesis synthesising the information in the three datasets was constructed following a total evidence approach and implementing dataset specific stepmatrices in order to correct for substitution biases. Pelargonium was found to consist of five main clades, some with contrasting evolutionary patterns with respect to biogeographic distributions, dispersal capacity, pollination biology and karyological diversification. The five main clades are structured in two (subgeneric) clades that correlate with chromosome size. One of these clades includes a "winter rainfall clade" containing more than 70% of all currently described Pelargonium species, and all restricted to the South African Cape winter rainfall region. Apart from (woody) shrubs and small herbaceous rosette subshrubs, this clade comprises a large "xerophytic" clade including geophytes, stem and leaf succulents, harbouring in total almost half of the genus. This clade is considered to be the result of in situ proliferation, possibly in response to late-Miocene and Pliocene aridification events. Nested within it is a radiation comprising c. 80 species from the geophytic Pelargonium section Hoarea, all characterised by the possession of (a series of) tunicate tubers.

alpha-Aminoisobutyric acid modified protected analogues of beta-amyloid residue 17-20: a change from sheet to helix

The strong intermolecular interactions mediated by short hydrophobic sequences (e.g., 17-20, -L-Leu-L-Val-L-Phe-L-Phe-) in the middle of A beta are known to play a crucial role in the neuropathology of Alzheimer's disease. FTIR, TEM and Congo red binding studies indicated that a series of L-Ala substituted terminally protected peptides related to the sequence 17-20 of the beta-amyloid peptide, adopted D-sheet conformations. However, the Aib-modified analogues disrupt the D-sheet structure and switch over to a 310 helix with increasing number of Aib residues. X-ray crystallography shed some light on the change from sheet to helix at atomic resolution. (c) 2006 Elsevier Ltd. All rights reserved.

Solution self-assembly of hybrid block copolymers containing poly(ethylene glycol) and amphiphilic beta-strand peptide sequences

The self-assembly in aqueous solution of hybrid block copolymers consisting of amphiphilic β-strand peptide sequences flanked by one or two PEG chains was investigated by means of circular dichroism spectroscopy, small-angle X-ray scattering, and transmission electron microscopy. In comparison with the native peptide sequence, it was found that the peptide secondary structure was stabilized against pH variation in the di-and tri-block copolymers with PEG. Small-angle X-ray scattering indicated the presence of fibrillar structures, the dimensions of which are comparable to the estimated width of a β-strand (with terminal PEG chains in the case of the copolymers). Transmission electron microscopy on selectively stained and dried specimens shows directly the presence of fibrils. It is proposed that these fibrils result from the hierarchical self-assembly of peptide β-strands into helical tapes, which then stack into fibrils.

The prompt hypothesis: clarification requests as corrective input for grammatical errors

The potential of clarification questions (CQs) to act as a form of corrective input for young children's grammatical errors was examined. Corrective responses were operationalized as those occasions when child speech shifted from erroneous to correct (E -> C) contingent on a clarification question. It was predicted that E -> C sequences would prevail over shifts in the opposite direction (C -> E), as can occur in the case of nonerror-contingent CQs. This prediction was tested via a standard intervention paradigm, whereby every 60s a sequence of two clarification requests (either specific or general) was introduced into conversation with a total of 45 2- and 4-year-old children. For 10 categories of grammatical structure, E -> C sequences predominated over their C -> E counterparts, with levels of E -> C shifts increasing after two clarification questions. Children were also more reluctant to repeat erroneous forms than their correct counterparts, following the intervention of CQs. The findings provide support for Saxton's prompt hypothesis, which predicts that error-contingent CQs bear the potential to cue recall of previously acquired grammatical forms.

Collaborative tele-rehabilitation: A strategy for increasing engagement

This paper examines the influence of a collaborative rehabilitation environment that encourages a long-distance collaborative "play" using two robot-mediated environments. This study presents a strategy for increasing motivation on able-bodied persons, applicable to impaired persons, to engage, sustain play and relate during a shared task. The study consisted of a series of eighteen single case studies, each involved in two distinct phases and assessed using a multidimensional measurement intended to assess participant' subjective experience. The results showed a clear positive trend in favour of the robot-mediated game environment. Subjects found the collaborative environment more valuable and more interesting and enjoyable. As a consequence, it appears subjects were willing to spend more time at a task.

Increasing detection rate of user-to-root attacks using genetic algorithms

An extensive set of machine learning and pattern classification techniques trained and tested on KDD dataset failed in detecting most of the user-to-root attacks. This paper aims to provide an approach for mitigating negative aspects of the mentioned dataset, which led to low detection rates. Genetic algorithm is employed to implement rules for detecting various types of attacks. Rules are formed of the features of the dataset identified as the most important ones for each attack type. In this way we introduce high level of generality and thus achieve high detection rates, but also gain high reduction of the system training time. Thenceforth we re-check the decision of the user-to- root rules with the rules that detect other types of attacks. In this way we decrease the false-positive rate. The model was verified on KDD 99, demonstrating higher detection rates than those reported by the state- of-the-art while maintaining low false-positive rate.