Generic GPCR residue numbers - aligning topology maps while minding the gaps.
Ontology highlight
ABSTRACT:
SUBMITTER: Isberg V
PROVIDER: S-EPMC4408928 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
Publications
Generic GPCR residue numbers - aligning topology maps while minding the gaps.
Isberg Vignir V de Graaf Chris C Bortolato Andrea A Cherezov Vadim V Katritch Vsevolod V Marshall Fiona H FH Mordalski Stefan S Pin Jean-Philippe JP Stevens Raymond C RC Vriend Gerrit G Gloriam David E DE
Trends in pharmacological sciences 20141222 1
Generic residue numbers facilitate comparisons of, for example, mutational effects, ligand interactions, and structural motifs. The numbering scheme by Ballesteros and Weinstein for residues within the class A GPCRs (G protein-coupled receptors) has more than 1100 citations, and the recent crystal structures for classes B, C, and F now call for a community consensus in residue numbering within and across these classes. Furthermore, the structural era has uncovered helix bulges and constrictions ...[more]
Similar Datasets
Project description:Retinotopic mapping, i.e., the mapping between visual inputs on the retina and neuronal activations in cortical visual areas, is one of the central topics in visual neuroscience. For human observers, the mapping is obtained by analyzing functional magnetic resonance imaging (fMRI) signals of cortical responses to slowly moving visual stimuli on the retina. Although it is well known from neurophysiology that the mapping is topological (i.e., the topology of neighborhood connectivity is preserved) within each visual area, retinotopic maps derived from the state-of-the-art methods are often not topological because of the low signal-to-noise ratio and spatial resolution of fMRI. The violation of topological condition is most severe in cortical regions corresponding to the neighborhood of the fovea (e.g., < 1 degree eccentricity in the Human Connectome Project (HCP) dataset), significantly impeding accurate analysis of retinotopic maps. This study aims to directly model the topological condition and generate topology-preserving and smooth retinotopic maps. Specifically, we adopted the Beltrami coefficient, a metric of quasiconformal mapping, to define the topological condition, developed a mathematical model to quantify topological smoothing as a constrained optimization problem, and elaborated an efficient numerical method to solve the problem. The method was then applied to V1, V2, and V3 simultaneously in the HCP dataset. Experiments with both simulated and real retinotopy data demonstrated that the proposed method could generate topological and smooth retinotopic maps.
| S-EPMC8360528 | biostudies-literature
Project description:Residue contacts predicted from correlated positions in a multiple sequence alignment are often sparse and uncertain. To some extent, these limitations in the data can be overcome by grouping the contacts by secondary structure elements and enumerating the possible packing arrangements of these elements in a combinatorial manner. Strong interactions appear frequently but inconsistent interactions are down-weighted and missing interactions up-weighted. The resulting improved consistency in the predicted interactions has allowed the method to be successfully applied to proteins up to 200 residues in length which is larger than any structure previously predicted using sequence data alone.
| S-EPMC3324774 | biostudies-literature
Project description:The Canadian Cancer Clinical Trials Network (3CTN, the Network), established in 2014 to address the decline in academic cancer clinical trials' (ACCT) activity, has successfully achieved incremental year-over-year accrual targets as well as implemented recognized performance measures and supports for improving efficiency and quality of trial activities at member sites across Canada. As part of efforts to address ongoing challenges of staff recruitment, retention, and turnover in academic institutions that have been more recently exacerbated by the pandemic, the Network's Performance Strategy Sub-Committee (PSC) oversaw surveys of site clinical research professionals intended to capture workforce development status and identify knowledge gaps using the Joint Task Force Core Competency Framework (JTF CCF) as the standard basis for assessment. Accountable to the 3CTN Management Committee, the PSC consists of clinical research operations experts across Canada responsible for overseeing implementation and monitoring progress of this initiative. Staff at 3CTN's adult sites evaluated and reported trial personnel core competencies and gaps according to each domain/leveled competency statement of the framework. The most frequently noted competency gaps were in the domains of: Investigational Product Development and Regulation (28%); Scientific Concepts and Research Design (16%); and Study and Site Management (14%). Reported data was compiled and represented in the 3CTN Core Competency Report, developed as a web-based, interactive tool enabling members and stakeholders to filter data to enumerate and quantify workforce competency gaps at their site, within their node of affiliated sites, or across the national Network. Concurrently, an environmental scan and review of education resources was conducted and reviewed by the PSC. Embedded links to curated learning and development resources were incorporated into the report and associated with each domain/leveled competency statement to provide ready access to high-quality learning and development resources where needed. In the remaining years of its current strategic plan, 3CTN will continue to monitor, develop collaborative initiatives to target prioritized clinical research competency gaps and create opportunities for ongoing assessment and reporting by sites to capture changes in workforce core competencies over time.
| S-EPMC10748401 | biostudies-literature
Project description:Beta-arrestins (?arrs) critically mediate desensitization, endocytosis and signalling of G protein-coupled receptors (GPCRs), and they scaffold a large number of interaction partners. However, allosteric modulation of their scaffolding abilities and direct targeting of their interaction interfaces to modulate GPCR functions selectively have not been fully explored yet. Here we identified a series of synthetic antibody fragments (Fabs) against different conformations of ?arrs from phage display libraries. Several of these Fabs allosterically and selectively modulated the interaction of ?arrs with clathrin and ERK MAP kinase. Interestingly, one of these Fabs selectively disrupted ?arr-clathrin interaction, and when expressed as an intrabody, it robustly inhibited agonist-induced endocytosis of a broad set of GPCRs without affecting ERK MAP kinase activation. Our data therefore demonstrate the feasibility of selectively targeting ?arr interactions using intrabodies and provide a novel framework for fine-tuning GPCR functions with potential therapeutic implications.
| S-EPMC5722207 | biostudies-literature
Project description:UnlabelledxiNET is a visualization tool for exploring cross-linking/mass spectrometry results. The interactive maps of the cross-link network that it generates are a type of node-link diagram. In these maps xiNET displays: (1) residue resolution positional information including linkage sites and linked peptides; (2) all types of cross-linking reaction product; (3) ambiguous results; and, (4) additional sequence information such as domains. xiNET runs in a browser and exports vector graphics which can be edited in common drawing packages to create publication quality figures.AvailabilityxiNET is open source, released under the Apache version 2 license. Results can be viewed by uploading data to http://crosslinkviewer.org/ or by downloading the software from http://github.com/colin-combe/crosslink-viewer and running it locally.
| S-EPMC4390258 | biostudies-literature
Project description:A variety of features are thought to contribute to the oligomeric and topological specificity of coiled coils. In previous work, we examined the determinants of oligomeric state. Here, we examine the energetic basis for the tendency of six coiled-coil peptides to align their α-helices in antiparallel orientation using molecular dynamics simulations with implicit solvation (EEF1.1). We also examine the effect of mutations known to disrupt the topology of these peptides. In agreement with experiment, ARG or LYS at a or d positions were found to stabilize the antiparallel configuration. The modeling suggests that this is not due to a-a' or d-d' repulsions but due to interactions with e' and g' residues. TRP at core positions also favors the antiparallel configuration. Residues that disfavor parallel dimers, such as ILE at d, are better tolerated in, and thus favor the antiparallel configuration. Salt bridge networks were found to be more stabilizing in the antiparallel configuration for geometric reasons: antiparallel helices point amino acid side chains in opposite directions. However, the structure with the largest number of salt bridges was not always the most stable, due to desolvation and configurational entropy contributions. In tetramers, the extent of stabilization of the antiparallel topology by core residues is influenced by the e' residue on a neighboring helix. Residues at b and c positions in some cases also contribute to stabilization of antiparallel tetramers. This work provides useful rules toward the goal of designing coiled coils with a well-defined and predictable three-dimensional structure.
| S-EPMC3267949 | biostudies-literature
Project description:Accurate prediction of atomic-level protein structure is important for annotating the biological functions of protein molecules and for designing new compounds to regulate the functions. Template-based modeling (TBM), which aims to construct structural models by copying and refining the structural frameworks of other known proteins, remains the most accurate method for protein structure prediction. Due to the difficulty in recognizing distant-homology templates, however, the accuracy of TBM decreases rapidly when the evolutionary relationship between the query and template vanishes. In this study, we propose a new method, CEthreader, which first predicts residue-residue contacts by coupling evolutionary precision matrices with deep residual convolutional neural-networks. The predicted contact maps are then integrated with sequence profile alignments to recognize structural templates from the PDB. The method was tested on two independent benchmark sets consisting collectively of 1,153 non-homologous protein targets, where CEthreader detected 176% or 36% more correct templates with a TM-score >0.5 than the best state-of-the-art profile- or contact-based threading methods, respectively, for the Hard targets that lacked homologous templates. Moreover, CEthreader was able to identify 114% or 20% more correct templates with the same Fold as the query, after excluding structures from the same SCOPe Superfamily, than the best profile- or contact-based threading methods. Detailed analyses show that the major advantage of CEthreader lies in the efficient coupling of contact maps with profile alignments, which helps recognize global fold of protein structures when the homologous relationship between the query and template is weak. These results demonstrate an efficient new strategy to combine ab initio contact map prediction with profile alignments to significantly improve the accuracy of template-based structure prediction, especially for distant-homology proteins.
| S-EPMC6818797 | biostudies-other
Project description:Current methods for whole-genome mapping of protein-DNA interactions, performed by coupling chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq), require large amounts of starting materials, which precludes their application to rare cell types. Here we combine a high-sensitivity ChIP assay with a new library preparation procedure to map histone modifications in as few as 10,000 cells. We used the technique to characterize mouse hematopoietic progenitors and thereby gain insight into their developmental program.
| S-EPMC2924612 | biostudies-literature
Project description:BackgroundStatistical information (e.g., on long-term survival or side effects) may be valuable for healthcare providers to share with their patients to facilitate shared decision making on treatment options. In this pre-registered study, we assessed cancer survivors' need for generic (population-based) versus personalized (tailored towards patient/tumor characteristics) statistical information after their diagnosis. We examined how information coping style, subjective numeracy, and anxiety levels of survivors relate to these needs and identified statistical need profiles. Additionally, we qualitatively explored survivors' considerations for (not) wanting statistical information.MethodsCancer survivors' need for statistics regarding incidence, survival, recurrence, side effects and quality of life were assessed with an online questionnaire. For each of these topics, survivors were asked to think back to their first cancer diagnosis and to indicate their need for generic and personalized statistics on a 4-point scale ('not at all'- 'very much'). Associations between information coping style, subjective numeracy, and anxiety with need for generic and personalized statistics were examined with Pearson's correlations. Statistical need profiles were identified using latent class analysis. Considerations for (not) wanting statistics were analyzed qualitatively.ResultsOverall, cancer survivors (n = 174) had a higher need for personalized than for generic statistics (p < .001, d = 0.74). Need for personalized statistics was associated with higher subjective numeracy (r = .29) and an information-seeking coping style (r = .41). Three statistical need profiles were identified (1) a strong need for both generic and personalized statistics (34%), (2) a stronger need for personalized than for generic statistics (55%), and (3) a little need for both generic and personalized statistics (11%). Considerations for wanting personalized cancer statistics ranged from feelings of being in control to making better informed decisions about treatment. Considerations for not wanting statistics related to negative experience with statistics and to the unpredictability of future events for individual patients.ConclusionsIn light of the increased possibilities for using personalized statistics in clinical practice and decision aids, it appears that most cancer survivors want personalized statistical information during treatment decision-making. Subjective numeracy and information coping style seem important factors influencing this need. We encourage further development and implementation of data-driven personalized decision support technologies in oncological care to support patients in treatment decision making.
| S-EPMC9535944 | biostudies-literature
Project description:Background Optical maps record locations of specific enzyme recognition sites within long genome fragments. This long-distance information enables aligning genome assembly contigs onto optical maps and ordering contigs into scaffolds. The generated scaffolds, however, often contain a large amount of gaps. To fill these gaps, a feasible way is to search genome assembly graph for the best-matching contig paths that connect boundary contigs of gaps. The combination of searching and evaluation procedures might be “searching followed by evaluation”, which is infeasible for long gaps, or “searching by evaluation”, which heavily relies on heuristics and thus usually yields unreliable contig paths. Results We here report an accurate and efficient approach to filling gaps of genome scaffolds with aids of optical maps. Using simulated data from 12 species and real data from 3 species, we demonstrate the successful application of our approach in gap filling with improved accuracy and completeness of genome scaffolds. Conclusion Our approach applies a sequential Bayesian updating technique to measure the similarity between optical maps and candidate contig paths. Using this similarity to guide path searching, our approach achieves higher accuracy than the existing “searching by evaluation” strategy that relies on heuristics. Furthermore, unlike the “searching followed by evaluation” strategy enumerating all possible paths, our approach prunes the unlikely sub-paths and extends the highly-probable ones only, thus significantly increasing searching efficiency. Supplementary Information The online version contains supplementary material available at 10.1186/s12859-021-04448-2.
| S-EPMC8557617 | biostudies-literature