EasyVS: a user friendly web based tool for molecule library selection and structure-based virtual screening

Summary: EasyVS is a web-based platform built to simplify molecule library selection and virtual screening. With an intuitive interface, the tool allows users to go from selecting a protein target with a known structure and tailoring a purchasable molecule library to performing and visualising docking in a few clicks. Our system also allows users to filter screening libraries based on molecule properties, cluster molecules by similarity and personalise docking parameters. Availability and implementation: EasyVS is freely available as an easy-to-use web interface at http://biosig.unimelb.edu.au/easyvsThis work has been supported by Melbourne Research Scholarships [to C.H.M.R and Y.M.]; Medical Research Council (MRC) [MR/M026302/1 to D.B.A., D.E.V.P.]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) - Finance Code 001 [to C.H.S.]; National Health and Medical Research Council of Australia [APP1072476 to D.B.A.]; Conselho Nacional de Desenvolvimento Cientı́fico e Tecnológico (CNPq) [to D.E.V.P. and C.H.S.]; Universidade Federal de Itajubá [to W.N.P.V. and C.H.S.]. Supported in part by the Victorian Government’s OIS Program

A new species of Colletes (Hymenoptera: Apoidea: Colletidae) from northern Florida and Georgia, with notes on the Colletes of those states

Colletes ultravalidus Hall & Ascher, new species, is described from several sites in northwestern Florida and southeastern Georgia.  It is a member of the inaequalis species group, very similar to C. validus Cresson, a specialist of Ericaceae, but can be distinguished by an even more elongate malar area and the absence of conspicuous tergal fascia.  Colletes ultravalidus has been found flying from early winter to early spring when it forms nest aggregations in xeric sites adjacent to shrub bog or basin swamp, the habitat of Pieris phyllyreifolia (Hook.) DC. (Ericaceae), the most likely, but as yet unconfirmed, host plant of the new species.  State records of Colletes for Florida and Georgia are reviewed and discrepancies in taxonomy and distributional limits between Stephen’s 1954 revision of the genus and Mitchell’s 1960 monograph of eastern North American bees are noted.  We concur with Stephen that the distributions of several taxa in Colletes are more limited than that reported by Mitchell

A Phenomenological Investigation Of Counseling Students\u27 And Practicum Supervisors\u27 Experiences With The Counselor Competencies Scale

Counselor educators are charged with facilitating the development of counseling students towards becoming ethical and competent counselors (American Counseling Association [ACA], 2005; Council for Accreditation for Counseling and Related Educational Programs [CACREP], 2009). In addition, counselor educators serve as gatekeepers for the profession and deny entry to counseling students who demonstrate deficiency of necessary competencies (ACA, 2005; Association for Counselor Education and Supervision [ACES], 1993; CACREP, 2009). Numerous assessment tools utilized for the evaluation of counseling competencies have been developed, yet none has gained universal acceptance in the field of counselor education. The Counseling Competencies Scale© (CCS, UCF Counselor Education Faculty, 2009) is a 32 item counseling-student assessment tool developed to measure counselors-in-training counselor competencies (counseling skills, professional dispositions, and behaviors). The psychometric properties of the CCS have been investigated (Swank, 2010); however, questions related to perceptions, purposes, and uses of the CCS remained. Therefore, the purpose of this descriptive, exploratory phenomenology was to understand counseling students‘ and practicum supervisors‘ lived experiences with the CCS. The sample included counseling practicum students (N = 23 [individual student interviews only, n = 11; student focus group interviews only, n = 4, individual student interviews and student focus group participants, n = 8]) and practicum supervisors (N = 6) from a CACREP accredited counselor education program in the Southeastern United States. The data was collected through individual interviews and focus groups with practicum students and individual interviews with practicum supervisors. All data was recorded, transcribed, coded, and analyzed for themes (Creswell, 2007; Moustakas, 1994). The data analyses utilized a research key iv comprised of 34 meaning units (Devenish, 2002; Moustakas, 1994) and identified five themes within the data: (a) Cognitive understanding, (b) Emotional Understanding, (c) Feedback, (d) Trustworthiness, and (e) Gatekeeping. A visual metaphor was developed to illustrate the interaction of the five themes. Trustworthiness measures employed throughout the research included the use of (a) descriptions of researcher positionality, (b) a self-reflective field journal, (c) triangulation (student and supervisor individual interviews, student focus group interviews, and examination of the CCS document), (d) member checking, (e) peer debriefers, (f) an external auditor, (g) an extensive description of previous literature, and (h) an openness to disconfirming evidence (Creswell, 2007; Marshall & Rossman, 2006; Moustakas, 1994). The results supported that counseling students and their clinical supervisors identified the CCS as an appropriate and comprehensive supervisory tool; however, they acknowledged CCSrelated limitations including inconsistent application, problematic scoring system, pass/fail structure, and delivery by instructors and practicum supervisors who demonstrated minimal investment of time and effort. Implications for counselor educators include the importance of program and faculty members‘ engagement and consistency regarding the use of (a) evaluation and feedback tools, (b) remediation and gatekeeping processes, and (c) counseling student performance expectations. Replication of this study at diverse institutions is suggested. In addition, quantitative and qualitative investigations examining counseling student competencies and development (e.g., CCS) would contribute to the counselor education, counseling-student development, and counseling supervision literature. A discussion of the investigation‘s limitations is included

mCSM-AB: a web server for predicting antibody-antigen affinity changes upon mutation with graph-based signatures.

Computational methods have traditionally struggled to predict the effect of mutations in antibody-antigen complexes on binding affinity. This has limited their usefulness during antibody engineering and development, and their ability to predict biologically relevant escape mutations. Here we present mCSM-AB, a user-friendly web server for accurately predicting antibody-antigen affinity changes upon mutation which relies on graph-based signatures. We show that mCSM-AB performs better than comparable methods that have been previously used for antibody engineering. mCSM-AB web server is available at http://structure.bioc.cam.ac.uk/mcsm_ab.This is the final published version. It first appeared at http://nar.oxfordjournals.org/content/early/2016/05/23/nar.gkw458.full

MTR-Viewer: Identifying regions within genes under purifying selection

Advances in genomic sequencing have enormous potential to revolutionise personalised medicine, however distinguishing disease-causing from benign variants remains a challenge. The increasing number of human genome and exome sequences available has revealed areas where unfavourable variation is removed through purifying selection. Here we present the MTR-Viewer, a web-server enabling easy visualisation at the gene or variant level of the Missense Tolerance Ratio (MTR), a measure of regional intolerance to missense variation calculated using variation from 220,000 exome and genome sequences. The MTR-Viewer enables exploration of MTR calculations, using different sliding windows, for over 18,000 human protein-coding genes and 85,000 alternative transcripts. Users can also view MTR scores calculated for specific ethnicities, to enable easy exploration of regions that may be under different selective pressure. The spatial distribution of population and known disease variants is also displayed on the protein’s domain structure. Intolerant regions were found to be highly enriched for ClinVar pathogenic and COSMIC somatic missense variants (Mann-Whitney U test p < 2.2x10-16). As the MTR is not biased by known domains and protein features, it can highlight functionally important regions within genes overlooked or inaccessible by traditional methods. MTR-Viewer is freely available via a user friendly web-server at http://biosig.unimelb.edu.au/mtr-viewer/.M.S. was supported by the Australian Government Research Training Program. S.P. was supported by an NHMRC R.D. Wright Career Development Fellowship (1126877). S.P. is an employee of AstraZeneca. D.B.A. was supported by the Jack Brockhoff Foundation [JBF 4186, 2016], a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) [MR/M026302/1]; the National Health and Medical Research Council of Australia [APP1072476]; and the Department of Biochemistry and Molecular Biology, University of Melbourne

Chandra Spectroscopy Of The Hot Star β Crucis And The Discovery Of A Pre-Main-Sequence Companion

In order to test the O star wind-shock scenario for X-ray production in less luminous stars with weaker winds, we made a pointed 74-ks observation of the nearby early B giant, beta Crucis (beta Cru; B0.5 III), with the Chandra High Energy Transmission Grating Spectrometer. We find that the X-ray spectrum is quite soft, with a dominant thermal component near 3 million K, and that the emission lines are resolved but quite narrow, with half widths of 150 km s(-1). The forbidden-to-intercombination line ratios of Ne IX and Mg XI indicate that the hot plasma is distributed in the wind, rather than confined near the photosphere. It is difficult to understand the X-ray data in the context of the standard wind-shock paradigm for OB stars, primarily because of the narrow lines, but also because of the high X-ray production efficiency. A scenario in which the bulk of the outer wind is shock heated is broadly consistent with the data, but not very well motivated theoretically. It is possible that magnetic channelling could explain the X-ray properties, although no field has been detected on beta Cru. We detected periodic variability in the hard (h nu \u3e 1 keV) X-rays, modulated on the known optical period of 4.58 h, which is the period of the primary beta Cephei pulsation mode for this star. We also have detected, for the first time, an apparent companion to beta Cru at a projected separation of 4 arcsec. This companion was likely never seen in optical images because of the presumed very high contrast between it and beta Cru in the optical. However, the brightness contrast in the X-ray is only 3:1, which is consistent with the companion being an X-ray active low-mass pre-main-sequence star. The companion\u27s X-ray spectrum is relatively hard and variable, as would be expected from a post-T Tauri star. The age of the beta Cru system (between 8 and 10 Myr) is consistent with this interpretation which, if correct, would add beta Cru to the roster of Lindroos binaries - B stars with low-mass pre-main-sequence companions

Chandra Spectroscopy Of The Hot Star β Crucis And The Discovery Of A Pre-Main-Sequence Companion

In order to test the O star wind-shock scenario for X-ray production in less luminous stars with weaker winds, we made a pointed 74-ks observation of the nearby early B giant, beta Crucis (beta Cru; B0.5 III), with the Chandra High Energy Transmission Grating Spectrometer. We find that the X-ray spectrum is quite soft, with a dominant thermal component near 3 million K, and that the emission lines are resolved but quite narrow, with half widths of 150 km s(-1). The forbidden-to-intercombination line ratios of Ne IX and Mg XI indicate that the hot plasma is distributed in the wind, rather than confined near the photosphere. It is difficult to understand the X-ray data in the context of the standard wind-shock paradigm for OB stars, primarily because of the narrow lines, but also because of the high X-ray production efficiency. A scenario in which the bulk of the outer wind is shock heated is broadly consistent with the data, but not very well motivated theoretically. It is possible that magnetic channelling could explain the X-ray properties, although no field has been detected on beta Cru. We detected periodic variability in the hard (h nu \u3e 1 keV) X-rays, modulated on the known optical period of 4.58 h, which is the period of the primary beta Cephei pulsation mode for this star. We also have detected, for the first time, an apparent companion to beta Cru at a projected separation of 4 arcsec. This companion was likely never seen in optical images because of the presumed very high contrast between it and beta Cru in the optical. However, the brightness contrast in the X-ray is only 3:1, which is consistent with the companion being an X-ray active low-mass pre-main-sequence star. The companion\u27s X-ray spectrum is relatively hard and variable, as would be expected from a post-T Tauri star. The age of the beta Cru system (between 8 and 10 Myr) is consistent with this interpretation which, if correct, would add beta Cru to the roster of Lindroos binaries - B stars with low-mass pre-main-sequence companions

Known allosteric proteins have central roles in genetic disease

Allostery is a form of protein regulation, where ligands that bind sites located apart from the active site can modify the activity of the protein. The molecular mechanisms of allostery have been extensively studied, because allosteric sites are less conserved than active sites, and drugs targeting them are more specific than drugs binding the active sites. Here we quantify the importance of allostery in genetic disease. We show that 1) known allosteric proteins are central in disease networks, and contribute to genetic disease and comorbidities much more than non-allosteric proteins, in many major disease types like hematopoietic diseases, cardiovascular diseases, cancers, diabetes, or diseases of the central nervous system. 2) variants from cancer genome-wide association studies are enriched near allosteric proteins, indicating their importance to polygenic traits; and 3) the importance of allosteric proteins in disease is due, at least partly, to their central positions in protein-protein interaction networks, and probably not due to their dynamical properties

DUET: a server for predicting effects of mutations on protein stability using an integrated computational approach.

Cancer genome and other sequencing initiatives are generating extensive data on non-synonymous single nucleotide polymorphisms (nsSNPs) in human and other genomes. In order to understand the impacts of nsSNPs on the structure and function of the proteome, as well as to guide protein engineering, accurate in silicomethodologies are required to study and predict their effects on protein stability. Despite the diversity of available computational methods in the literature, none has proven accurate and dependable on its own under all scenarios where mutation analysis is required. Here we present DUET, a web server for an integrated computational approach to study missense mutations in proteins. DUET consolidates two complementary approaches (mCSM and SDM) in a consensus prediction, obtained by combining the results of the separate methods in an optimized predictor using Support Vector Machines (SVM). We demonstrate that the proposed method improves overall accuracy of the predictions in comparison with either method individually and performs as well as or better than similar methods. The DUET web server is freely and openly available at http://structure.bioc.cam.ac.uk/duet