WEBnm@: a web application for normal mode analyses of proteins

BACKGROUND: Normal mode analysis (NMA) has become the method of choice to investigate the slowest motions in macromolecular systems. NMA is especially useful for large biomolecular assemblies, such as transmembrane channels or virus capsids. NMA relies on the hypothesis that the vibrational normal modes having the lowest frequencies (also named soft modes) describe the largest movements in a protein and are the ones that are functionally relevant. RESULTS: We developed a web-based server to perform normal modes calculations and different types of analyses. Starting from a structure file provided by the user in the PDB format, the server calculates the normal modes and subsequently offers the user a series of automated calculations; normalized squared atomic displacements, vector field representation and animation of the first six vibrational modes. Each analysis is performed independently from the others and results can be visualized using only a web browser. No additional plug-in or software is required. For users who would like to analyze the results with their favorite software, raw results can also be downloaded. The application is available on . We present here the underlying theory, the application architecture and an illustration of its features using a large transmembrane protein as an example. CONCLUSION: We built an efficient and modular web application for normal mode analysis of proteins. Non specialists can easily and rapidly evaluate the degree of flexibility of multi-domain protein assemblies and characterize the large amplitude movements of their domains

Implementering av objektdeteksjon på maritim dronesverm. Bruk av kunstig intelligens til maritim overvåkning på ubemannede fartøy

Norge har verdens nest lengste kyst og det er dermed utfordrende å opprettholde situa-sjonsforståelse langs kysten til enhver tid. Samtidig er det signalisert i Langtidsplanen for Forsvaret at antallet bemannede fartøy vil reduseres (Hareide, Relling, Pettersen, Sauter, & Mjelde, 2018). For å bedre situasjonsforståelsen kan ubemannede overflate-fartøy bli benyttet. Likevel vil enkeltenheter bare kunne dekke enkeltområder av gangen. Et godt alternativ er da sverm. Tre eller flere enheter som jobber sammen for å gjennomføre arbeidsoppgaver. I 2019 ble det utviklet en testplattform for dronesverm (Hellesnes & Lyssand, 2019). Konseptet kan føre til dekning i store områder om enhe-tene jobber sammen for å løse en oppgave. Sammenhengen mellom et behov for situa-sjonsforståelse langs kysten og svermoppgaven fra 2019 fører oss inn på vår problems-tilling: Hvordan kan objektgjenkjenning implementeres på dronesvermer for å gjøre de-teksjoner og identifikasjoner av fartøy? Prosjektet har utviklet et konsept for maritim overvåkning på dronesverm gjennom bruk av objektdeteksjon. For å bevise konseptet har vi videretrent en maskinlæringsmodell til å gjenkjenne en egendefinert fartøysklasse. Resultatene fra testen har vært lovende og vist at avansert teknologi kan anvendes med begrensede ressurser innenfor objektdeteksjons-feltet. Oppgaven har også belyst hvor avhengig objektdeteksjonsmodeller er på endringer av miljø. Det anbefales derfor å starte å bygge opp datasett med bilder av norskekysten og på fartøy av interesse, slik at Sjøforsvaret er klar for implementering av lignende tek-nologi i fremtiden. Videre benytter prosjektet data fra maskinlæringsmodellen til å regne ut relativ peiling. Dette gjør det mulig for enhetene i svermen å kunne lokalisere detekterte fartøy. Denne informasjonen blir deretter delt med de andre svermenhetene. Det kan derfor tenkes at sammensetninger av relative peilinger, kan benyttes for å finne absolutt posisjon på et detektert fartøy. En svermalgoritme som legger til rette for dette er enda ikke laget og anbefales som videre arbeid fra dette prosjektet

WEBnm@ v2.0: Web server and services for comparing protein flexibility

Background: Normal mode analysis (NMA) using elastic network models is a reliable and cost-effective computational method to characterise protein flexibility and by extension, their dynamics. Further insight into the dynamics–function relationship can be gained by comparing protein motions between protein homologs and functional classifications. This can be achieved by comparing normal modes obtained from sets of evolutionary related proteins. Results: We have developed an automated tool for comparative NMA of a set of pre-aligned protein structures. The user can submit a sequence alignment in the FASTA format and the corresponding coordinate files in the Protein Data Bank (PDB) format. The computed normalised squared atomic fluctuations and atomic deformation energies of the submitted structures can be easily compared on graphs provided by the web user interface. The web server provides pairwise comparison of the dynamics of all proteins included in the submitted set using two measures: the Root Mean Squared Inner Product and the Bhattacharyya Coefficient. The Comparative Analysis has been implemented on our web server for NMA, WEBnm@, which also provides recently upgraded functionality for NMA of single protein structures. This includes new visualisations of protein motion, visualisation of inter-residue correlations and the analysis of conformational change using the overlap analysis. In addition, programmatic access to WEBnm@ is now available through a SOAP-based web service. Webnm@ is available at http://apps.cbu.uib.no/webnma. Conclusion: WEBnm@ v2.0 is an online tool offering unique capability for comparative NMA on multiple protein structures. Along with a convenient web interface, powerful computing resources, and several methods for mode analyses, WEBnm@ facilitates the assessment of protein flexibility within protein families and superfamilies. These analyses can give a good view of how the structures move and how the flexibility is conserved over the different structures.publishedVersio

Innovation in values based public health nursing student selection: a qualitative evaluation of candidate and selection panel member perspectives

Values based recruitment emerges from the premise that a high degree of valuecongruence, or the extent to which an individual’s values are similar to those of the health organisation in which they work, leads to organisational effectiveness. Objectives: The aim of this evaluation was to explore how candidates and selection panel members experienced and perceived innovative methods of values based public health nursing student selection. Intervention: The use of photo elicitation interviews and situational judgement questions in the context of selection to a university run public health nursing educational programme was explored. Design: The evaluation was framed by a qualitative exploratory design involving semistructured interviews and a group exercise. Data were thematically analysed. Sample: Eight semi-structured interviews were conducted with selection panel members. Twenty-two successful candidates took part in a group exercise. Results: Whilst candidates were ambivalent about the use of photo elicitation interviews, with some misunderstanding the task, selection panel members saw the benefits for improving candidate expression and reducing gaming and deception. Situational interview questions were endorsed by candidates and selection panel members due to their fidelity to real life problems and the ability of panel members to discern value congruence from candidates’ responses

Place fields and the cognitive map

The discovery of place cells by John O'Keefe in the early 1970s was a breakthrough not just for systems neuroscience, but also for psychology: place fields provided a clear neural substrate for the notion of a cognitive map, a construct devised to explain rat learning and spatial cognition. However, is the robust location-related firing of place cells still best conceptualised as a cognitive map? In this commentary, we reassess this view of hippocampus function in light of subsequent findings on place cells. We argue that as place fields encode local space, and as they are modulated by ongoing behavior, the representation they provide may be more cognitive than map-like

Replay as wavefronts and theta sequences as bump oscillations in a grid cell attractor network.

Grid cells fire in sequences that represent rapid trajectories in space. During locomotion, theta sequences encode sweeps in position starting slightly behind the animal and ending ahead of it. During quiescence and slow wave sleep, bouts of synchronized activity represent long trajectories called replays, which are well-established in place cells and have been recently reported in grid cells. Theta sequences and replay are hypothesized to facilitate many cognitive functions, but their underlying mechanisms are unknown. One mechanism proposed for grid cell formation is the continuous attractor network. We demonstrate that this established architecture naturally produces theta sequences and replay as distinct consequences of modulating external input. Driving inhibitory interneurons at the theta frequency causes attractor bumps to oscillate in speed and size, which gives rise to theta sequences and phase precession, respectively. Decreasing input drive to all neurons produces traveling wavefronts of activity that are decoded as replays

Author response

Discrete populations of brain cells signal heading direction, rather like a compass. These ‘head direction’ cells are largely confined to a closely-connected network of sites. We describe, for the first time, a population of head direction cells in nucleus reuniens of the thalamus in the freely-moving rat. This novel subcortical head direction signal potentially modulates the hippocampal CA fields directly and, thus, informs spatial processing and memor

oGNM: online computation of structural dynamics using the Gaussian Network Model

An assessment of the equilibrium dynamics of biomolecular systems, and in particular their most cooperative fluctuations accessible under native state conditions, is a first step towards understanding molecular mechanisms relevant to biological function. We present a web-based system, oGNM that enables users to calculate online the shape and dispersion of normal modes of motion for proteins, oligonucleotides and their complexes, or associated biological units, using the Gaussian Network Model (GNM). Computations with the new engine are 5–6 orders of magnitude faster than those using conventional normal mode analyses. Two cases studies illustrate the utility of oGNM. The first shows that the thermal fluctuations predicted for 1250 non-homologous proteins correlate well with X-ray crystallographic data over a broad range [7.3–15 Å] of inter-residue interaction cutoff distances and the correlations improve with increasing observation temperatures. The second study, focused on 64 oligonucleotides and oligonucleotide–protein complexes, shows that good agreement with experiments is achieved by representing each nucleotide by three GNM nodes (as opposed to one-node-per-residue in proteins) along with uniform interaction ranges for all components of the complexes. These results open the way to a rapid assessment of the dynamics of DNA/RNA-containing complexes. The server can be accessed at

Wordom: A User-Friendly Program for the Analysis of Molecular Structures, Trajectories, and Free Energy Surfaces

Wordom is a versatile, user-friendly, and efficient program for manipulation and analysis of molecular structures and dynamics. The following new analysis modules have been added since the publication of the original Wordom paper in 2007: assignment of secondary structure, calculation of solvent accessible surfaces, elastic network model, motion cross correlations, protein structure network, shortest intra-molecular and inter-molecular communication paths, kinetic grouping analysis, and calculation of mincut-based free energy profiles. In addition, an interface with the Python scripting language has been built and the overall performance and user accessibility enhanced. The source code of Wordom (in the C programming language) as well as documentation for usage and further development are available as an open source package under the GNU General Purpose License from http://wordom.sf.net. © 2010 Wiley Periodicals, Inc. J Comput Chem, 201

Evolutionary inaccuracy of pairwise structural alignments

Motivation: Structural alignment methods are widely used to generate gold standard alignments for improving multiple sequence alignments and transferring functional annotations, as well as for assigning structural distances between proteins. However, the correctness of the alignments generated by these methods is difficult to assess objectively since little is known about the exact evolutionary history of most proteins. Since homology is an equivalence relation, an upper bound on alignment quality can be found by assessing the consistency of alignments. Measuring the consistency of current methods of structure alignment and determining the causes of inconsistencies can, therefore, provide information on the quality of current methods and suggest possibilities for further improvement