PocketMatch: A new algorithm to compare binding sites in protein structures

Background: Recognizing similarities and deriving relationships among protein molecules is a fundamental
requirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One of
the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison.

Results: Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariant
manner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unless
combined with chemical nature of amino acids.

Conclusions: A new algorithm has been developed to compare binding sites in accurate, efficient and
high-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that along
with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250th second for one comparison on a single processor. A parallel version on BlueGene has also been implemented

SSMap: A new UniProt-PDB mapping resource for the curation of structural-related information in the UniProt/Swiss-Prot Knowledgebase

<p>Abstract</p> <p>Background</p> <p>Sequences and structures provide valuable complementary information on protein features and functions. However, it is not always straightforward for users to gather information concurrently from the sequence and structure levels. The UniProt knowledgebase (UniProtKB) strives to help users on this undertaking by providing complete cross-references to Protein Data Bank (PDB) as well as coherent feature annotation using available structural information. In this study, SSMap – a new UniProt-PDB residue-residue level mapping – was generated. The primary objective of this mapping is not only to facilitate the two tasks mentioned above, but also to palliate a number of shortcomings of existent mappings. SSMap is the first isoform sequence-specific mapping resource and is up-to-date for UniProtKB annotation tasks. The method employed by SSMap differs from the other mapping resources in that it stresses on the correct reconstruction of the PDB sequence from structures, and on the correct attribution of a UniProtKB entry to each PDB chain by using a series of post-processing steps.</p> <p>Results</p> <p>SSMap was compared to other existing mapping resources in terms of the correctness of the attribution of PDB chains to UniProtKB entries, and of the quality of the pairwise alignments supporting the residue-residue mapping. It was found that SSMap shared about 80% of the mappings with other mapping sources. New and alternative mappings proposed by SSMap were mostly good as assessed by manual verification of data subsets. As for local pairwise alignments, it was shown that major discrepancies (both in terms of alignment lengths and boundaries), when present, were often due to differences in methodologies used for the mappings.</p> <p>Conclusion</p> <p>SSMap provides an independent, good quality UniProt-PDB mapping. The systematic comparison conducted in this study allows the further identification of general problems in UniProt-PDB mappings so that both the coverage and the quality of the mappings can be systematically improved for the benefit of the scientific community. SSMap mapping is currently used to provide PDB cross-references in UniProtKB.</p

Energy spectra of quantum rings

Ring geometries have fascinated experimental and theoretical physicists over many years. Open rings connected to leads allow the observation of the Aharonov-Bohm effect, a paradigm of quantum mechanical phase coherence. The phase coherence of transport through a quantum dot embedded in one arm of an open ring has been demonstrated. The energy spectrum of closed rings has only recently been analysed by optical experiments and is the basis for the prediction of persistent currents and related experiments. Here we report magnetotransport experiments on a ring-shaped semiconductor quantum dot in the Coulomb blockade regime. The measurements allow us to extract the discrete energy levels of a realistic ring, which are found to agree well with theoretical expectations. Such an agreement, so far only found for few-electron quantum dots, is here extended to a many-electron system. In a semiclassical language our results indicate that electron motion is governed by regular rather than chaotic motion, an unexplored regime in many-electron quantum dots.Comment: 10 pages, 4 figure

Identification of a protein encoded in the EB-viral open reading frame BMRF2

Using monospecific rabbit sera against a peptide derived from a potential antigenic region of the Epstein-Barr viral amino acid sequence encoded in the open reading frame BMRF2 we could identify a protein-complex of 53/55 kDa in chemically induced B95-8, P3HR1 and Raji cell lines. This protein could be shown to be membrane-associated, as predicted by previous computer analysis of the secondary structure and hydrophilicity pattern, and may be a member of EBV-induced membrane proteins in lytically infected cells

FLORA: a novel method to predict protein function from structure in diverse superfamilies

Predicting protein function from structure remains an active area of interest, particularly for the structural genomics initiatives where a substantial number of structures are initially solved with little or no functional characterisation. Although global structure comparison methods can be used to transfer functional annotations, the relationship between fold and function is complex, particularly in functionally diverse superfamilies that have evolved through different secondary structure embellishments to a common structural core. The majority of prediction algorithms employ local templates built on known or predicted functional residues. Here, we present a novel method (FLORA) that automatically generates structural motifs associated with different functional sub-families (FSGs) within functionally diverse domain superfamilies. Templates are created purely on the basis of their specificity for a given FSG, and the method makes no prior prediction of functional sites, nor assumes specific physico-chemical properties of residues. FLORA is able to accurately discriminate between homologous domains with different functions and substantially outperforms (a 2–3 fold increase in coverage at low error rates) popular structure comparison methods and a leading function prediction method. We benchmark FLORA on a large data set of enzyme superfamilies from all three major protein classes (α, β, αβ) and demonstrate the functional relevance of the motifs it identifies. We also provide novel predictions of enzymatic activity for a large number of structures solved by the Protein Structure Initiative. Overall, we show that FLORA is able to effectively detect functionally similar protein domain structures by purely using patterns of structural conservation of all residues

Interaction of perceptual grouping and crossmodal temporal capture in tactile apparent-motion

Previous studies have shown that in tasks requiring participants to report the direction of apparent motion, task-irrelevant mono-beeps can &quot;capture'' visual motion perception when the beeps occur temporally close to the visual stimuli. However, the contributions of the relative timing of multimodal events and the event structure, modulating uni- and/or crossmodal perceptual grouping, remain unclear. To examine this question and extend the investigation to the tactile modality, the current experiments presented tactile two-tap apparent-motion streams, with an SOA of 400 ms between successive, left-/right-hand middle-finger taps, accompanied by task-irrelevant, non-spatial auditory stimuli. The streams were shown for 90 seconds, and participants' task was to continuously report the perceived (left-or rightward) direction of tactile motion. In Experiment 1, each tactile stimulus was paired with an auditory beep, though odd-numbered taps were paired with an asynchronous beep, with audiotactile SOAs ranging from -75 ms to 75 ms. Perceived direction of tactile motion varied systematically with audiotactile SOA, indicative of a temporal-capture effect. In Experiment 2, two audiotactile SOAs-one short (75 ms), one long (325 ms)-were compared. The long-SOA condition preserved the crossmodal event structure (so the temporal-capture dynamics should have been similar to that in Experiment 1), but both beeps now occurred temporally close to the taps on one side (even-numbered taps). The two SOAs were found to produce opposite modulations of apparent motion, indicative of an influence of crossmodal grouping. In Experiment 3, only odd-numbered, but not even-numbered, taps were paired with auditory beeps. This abolished the temporal-capture effect and, instead, a dominant percept of apparent motion from the audiotactile side to the tactile-only side was observed independently of the SOA variation. These findings suggest that asymmetric crossmodal grouping leads to an attentional modulation of apparent motion, which inhibits crossmodal temporal-capture effects

Double Field Theory for Double D-branes

We consider Hull's doubled formalism for open strings on D-branes in flat space and construct the corresponding effective double field theory. We show that the worldsheet boundary conditions of the doubled formalism describe in a unified way a T-dual pair of D-branes, which we call double D-branes. We evaluate the one-loop beta function for the boundary gauge coupling and then obtain the effective field theory for the double D-branes. The effective field theory is described by a DBI action of double fields. The T-duality covariant form of this DBI action is thus a kind of "master" action, which describes all the double D-brane configurations related by T-duality transformations. We discuss a number of aspects of this effective theory.Comment: Latex, 1+33 pages. v2 with minor corrections, a new reference added. v3 a typo correcte

Molecular Modeling of the Interaction Between Stem Cell Peptide and Immune Receptor in Plants

© Springer Science+Business Media, LLC, part of Springer Nature 2020. Molecular docking enables comprehensive exploration of interactions between chemical moieties and proteins. Modeling and docking approaches are useful to determine the three-dimensional (3D) structure of experimentally uncrystallized proteins and subsequently their interactions with various inhibitors and activators or peptides. Here, we describe a protocol for carrying out molecular modeling and docking of stem cell peptide CLV3p on plant innate immune receptor FLS2

Systematic reviews of complementary therapies - an annotated bibliography. Part 1: Acupuncture

Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with acupuncture. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of acupuncture; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. Results From a total of 48 potentially relevant reviews preselected in a screeening process 39 met the inclusion criteria. 22 were on various pain syndromes or rheumatic diseases. Other topics addressed by more than one review were addiction, nausea, asthma and tinnitus. Almost unanimously the reviews state that acupuncture trials include too few patients. Often included trials are heterogeneous regarding patients, interventions and outcome measures, are considered to have insufficient quality and contradictory results. Convincing evidence is available only for postoperative nausea, for which acupuncture appears to be of benefit, and smoking cessation, where acupuncture is no more effective than sham acupuncture. Conclusions A large number of systematic reviews on acupuncture exists. What is most obvious from these reviews is the need for (the funding of) well-designed, larger clinical trials

Maternal Condition Does Not Influence Birth Sex Ratios in Anubis Baboons (Papio anubis)

Trivers and Willard predicted that when parental condition has differential effects on the fitness of male and female offspring, parents who are in good condition will bias investment toward the sex that benefits most from additional investment. Efforts to test predictions derived from Trivers and Willard's model have had mixed results, perhaps because most studies have relied on proxy measures of parental condition, such as dominance rank. Here, we examine the effects of female baboons condition on birth sex ratios and post-natal investment, based on visual assessments of maternal body condition. We find that local environmental conditions have significant effects on female condition, but maternal condition at conception has no consistent relationship with birth sex ratios. Mothers who are in poorer condition at the time of conception resume cycling significantly later than females who are in better condition, but the sex of their infants has no effect on the time to resumption of cycling. Thus, our findings provide strong evidence that maternal condition influences females' ability to reproduce, but females do not facultatively adjust the sex ratio of their offspring in relation to their dominance rank or current condition