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Konstantin Arnold

Bio: Konstantin Arnold is an academic researcher from Swiss Institute of Bioinformatics. The author has contributed to research in topics: Protein structure database & Structural genomics. The author has an hindex of 11, co-authored 15 publications receiving 15605 citations. Previous affiliations of Konstantin Arnold include Rutgers University & University of Basel.

Papers
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Journal ArticleDOI
TL;DR: The SWISS-MODEL workspace is a web-based integrated service dedicated to protein structure homology modelling that assists and guides the user in building protein homology models at different levels of complexity.
Abstract: Motivation: Homology models of proteins are of great interest for planning and analysing biological experiments when no experimental three-dimensional structures are available. Building homology models requires specialized programs and up-to-date sequence and structural databases. Integrating all required tools, programs and databases into a single web-based workspace facilitates access to homology modelling from a computer with web connection without the need of downloading and installing large program packages and databases. Results: SWISS-MODEL workspace is a web-based integrated service dedicated to protein structure homology modelling. It assists and guides the user in building protein homology models at different levels of complexity. A personal working environment is provided for each user where several modelling projects can be carried out in parallel. Protein sequence and structure databases necessary for modelling are accessible from the workspace and are updated in regular intervals. Tools for template selection, model building and structure quality evaluation can be invoked from within the workspace. Workflow and usage of the workspace are illustrated by modelling human Cyclin A1 and human Transmembrane Protease 3. Availability: The SWISS-MODEL workspace can be accessed freely at http://swissmodel.expasy.org/workspace/ Contact: Torsten.Schwede@unibas.ch Supplementary information: Supplementary data are available at Bioinformatics online.

7,107 citations

Journal ArticleDOI
TL;DR: The latest version of the SWISS-MODEL expert system for protein structure modelling is described, which makes extensive use of model quality estimation for selection of the most suitable templates and provides estimates of the expected accuracy of the resulting models.
Abstract: Protein structure homology modelling has become a routine technique to generate 3D models for proteins when experimental structures are not available. Fully automated servers such as SWISS-MODEL with user-friendly web interfaces generate reliable models without the need for complex software packages or downloading large databases. Here, we describe the latest version of the SWISS-MODEL expert system for protein structure modelling. The SWISS-MODEL template library provides annotation of quaternary structure and essential ligands and co-factors to allow for building of complete structural models, including their oligomeric structure. The improved SWISS-MODEL pipeline makes extensive use of model quality estimation for selection of the most suitable templates and provides estimates of the expected accuracy of the resulting models. The accuracy of the models generated by SWISS-MODEL is continuously evaluated by the CAMEO system. The new web site allows users to interactively search for templates, cluster them by sequence similarity, structurally compare alternative templates and select the ones to be used for model building. In cases where multiple alternative template structures are available for a protein of interest, a user-guided template selection step allows building models in different functional states. SWISS-MODEL is available at http://swissmodel.expasy.org/.

4,235 citations

Journal ArticleDOI
TL;DR: The aim of the SWISS-MODEL Repository is to provide access to an up-to-date collection of annotated 3D protein models generated by automated homology modelling for all sequences in Swiss-Prot and for relevant models organisms.
Abstract: SWISS-MODEL Repository (http://swissmodel.expasy.org/repository/) is a database of 3D protein structure models generated by the SWISS-MODEL homology-modelling pipeline. The aim of the SWISS-MODEL Repository is to provide access to an up-to-date collection of annotated 3D protein models generated by automated homology modelling for all sequences in Swiss-Prot and for relevant models organisms. Regular updates ensure that target coverage is complete, that models are built using the most recent sequence and template structure databases, and that improvements in the underlying modelling pipeline are fully utilised. As of September 2008, the database contains 3.4 million entries for 2.7 million different protein sequences from the UniProt database. SWISS-MODEL Repository allows the users to assess the quality of the models in the database, search for alternative template structures, and to build models interactively via SWISS-MODEL Workspace (http://swissmodel.expasy.org/workspace/). Annotation of models with functional information and cross-linking with other databases such as the Protein Model Portal (http://www.proteinmodelportal.org) of the PSI Structural Genomics Knowledge Base facilitates the navigation between protein sequence and structure resources.

1,942 citations

Journal ArticleDOI
TL;DR: The new web interface provides, in particular, visual guidance for newcomers to ExPASy, becoming an extensible and integrative portal accessing many scientific resources, databases and software tools in different areas of life sciences.
Abstract: ExPASy (http://www.expasy.org) has worldwide reputation as one of the main bioinformatics resources for proteomics. It has now evolved, becoming an extensible and integrative portal accessing many scientific resources, databases and software tools in different areas of life sciences. Scientists can henceforth access seamlessly a wide range of resources in many different domains, such as proteomics, genomics, phylogeny/evolution, systems biology, population genetics, transcriptomics, etc. The individual resources (databases, web-based and downloadable software tools) are hosted in a 'decentralized' way by different groups of the SIB Swiss Institute of Bioinformatics and partner institutions. Specifically, a single web portal provides a common entry point to a wide range of resources developed and operated by different SIB groups and external institutions. The portal features a search function across 'selected' resources. Additionally, the availability and usage of resources are monitored. The portal is aimed for both expert users and people who are not familiar with a specific domain in life sciences. The new web interface provides, in particular, visual guidance for newcomers to ExPASy.

1,665 citations

Journal ArticleDOI
TL;DR: Homology modeling aims to build three-dimensional protein structure models using experimentally determined structures of related family members as templates to generate reliable structural models and is routinely used in many biological applications.
Abstract: Homology modeling aims to build three-dimensional protein structure models using experimentally determined structures of related family members as templates. SWISS-MODEL workspace is an integrated Web-based modeling expert system. For a given target protein, a library of experimental protein structures is searched to identify suitable templates. On the basis of a sequence alignment between the target protein and the template structure, a three-dimensional model for the target protein is generated. Model quality assessment tools are used to estimate the reliability of the resulting models. Homology modeling is currently the most accurate computational method to generate reliable structural models and is routinely used in many biological applications. Typically, the computational effort for a modeling project is less than 2 h. However, this does not include the time required for visualization and interpretation of the model, which may vary depending on personal experience working with protein structures.

1,194 citations


Cited by
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Journal ArticleDOI
TL;DR: An updated protocol for Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants for a user's protein sequence.
Abstract: Phyre2 is a web-based tool for predicting and analyzing protein structure and function. Phyre2 uses advanced remote homology detection methods to build 3D models, predict ligand binding sites, and analyze amino acid variants in a protein sequence. Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2 . A typical structure prediction will be returned between 30 min and 2 h after submission.

7,941 citations

Journal ArticleDOI
TL;DR: An update to the SWISS-MODEL server is presented, which includes the implementation of a new modelling engine, ProMod3, and the introduction a new local model quality estimation method, QMEANDisCo.
Abstract: Homology modelling has matured into an important technique in structural biology, significantly contributing to narrowing the gap between known protein sequences and experimentally determined structures. Fully automated workflows and servers simplify and streamline the homology modelling process, also allowing users without a specific computational expertise to generate reliable protein models and have easy access to modelling results, their visualization and interpretation. Here, we present an update to the SWISS-MODEL server, which pioneered the field of automated modelling 25 years ago and been continuously further developed. Recently, its functionality has been extended to the modelling of homo- and heteromeric complexes. Starting from the amino acid sequences of the interacting proteins, both the stoichiometry and the overall structure of the complex are inferred by homology modelling. Other major improvements include the implementation of a new modelling engine, ProMod3 and the introduction a new local model quality estimation method, QMEANDisCo. SWISS-MODEL is freely available at https://swissmodel.expasy.org.

7,022 citations

01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

Journal ArticleDOI
TL;DR: A stand-alone I-TASSER Suite that can be used for off-line protein structure and function prediction and three complementary algorithms to enhance function inferences are developed, the consensus of which is derived by COACH4 using support vector machines.
Abstract: The lowest free-energy conformations are identified by structure clustering. A second round of assembly simulation is conducted, starting from the centroid models, to remove steric clashes and refine global topology. Final atomic structure models are constructed from the low-energy conformations by a two-step atomic-level energy minimization approach. The correctness of the global model is assessed by the confidence score, which is based on the significance of threading alignments and the density of structure clustering; the residue-level local quality of the structural models and B factor of the target protein are evaluated by a newly developed method, ResQ, built on the variation of modeling simulations and the uncertainty of homologous alignments through support vector regression training. For function annotation, the structure models with the highest confidence scores are matched against the BioLiP5 database of ligand-protein interactions to detect homologous function templates. Functional insights on ligand-binding site (LBS), Enzyme Commission (EC) and Gene Ontology (GO) are deduced from the functional templates. We developed three complementary algorithms (COFACTOR, TM-SITE and S-SITE) to enhance function inferences, the consensus of which is derived by COACH4 using support vector machines. Detailed instructions for installation, implementation and result interpretation of the Suite can be found in the Supplementary Methods and Supplementary Tables 1 and 2. The I-TASSER Suite pipeline was tested in recent communitywide structure and function prediction experiments, including CASP10 (ref. 1) and CAMEO2. Overall, I-TASSER generated the correct fold with a template modeling score (TM-score) >0.5 for 10 out of 36 “New Fold” (NF) targets in the CASP10, which have no homologous templates in the Protein Data Bank (PDB). Of the 110 template-based modeling targets, 92 had a TM-score >0.5, and 89 had the templates drawn closer to the native with an average r.m.s. deviation improvement of 1.05 Å in the same threadingaligned regions6. In CAMEO, COACH generated LBS predictions for 4,271 targets with an average accuracy 0.86, which was 20% higher than that of the second-best method in the experiment. Here we illustrate I-TASSER Suite–based structure and function modeling using six examples (Fig. 1b–g) from the communitywide blind tests1,2. R0006 and R0007 are two NF targets from CASP10, and I-TASSER constructed models of correct fold with a TM-score of 0.62 for both targets (Fig. 1b,c). An illustration of local quality estimation by ResQ is shown for T0652, which has an average error 0.75 Å compared to the actual deviation of the model from the native (Fig. 1h). The four LBS prediction examples (Fig. 1d–g) are from CASP10 (ref. 1) and CAMEO2; COACH generated ligand models all with a ligand r.m.s. deviation below 2 Å. COACH also correctly assigned the threeand fourdigit EC numbers to the enzyme targets C0050 and C0046 (Supplementary Table 3). In summary, we developed a stand-alone I-TASSER Suite that can be used for off-line protein structure and function prediction. The I-TASSER Suite: protein structure and function prediction

4,693 citations

Journal ArticleDOI
TL;DR: The latest version of the SWISS-MODEL expert system for protein structure modelling is described, which makes extensive use of model quality estimation for selection of the most suitable templates and provides estimates of the expected accuracy of the resulting models.
Abstract: Protein structure homology modelling has become a routine technique to generate 3D models for proteins when experimental structures are not available. Fully automated servers such as SWISS-MODEL with user-friendly web interfaces generate reliable models without the need for complex software packages or downloading large databases. Here, we describe the latest version of the SWISS-MODEL expert system for protein structure modelling. The SWISS-MODEL template library provides annotation of quaternary structure and essential ligands and co-factors to allow for building of complete structural models, including their oligomeric structure. The improved SWISS-MODEL pipeline makes extensive use of model quality estimation for selection of the most suitable templates and provides estimates of the expected accuracy of the resulting models. The accuracy of the models generated by SWISS-MODEL is continuously evaluated by the CAMEO system. The new web site allows users to interactively search for templates, cluster them by sequence similarity, structurally compare alternative templates and select the ones to be used for model building. In cases where multiple alternative template structures are available for a protein of interest, a user-guided template selection step allows building models in different functional states. SWISS-MODEL is available at http://swissmodel.expasy.org/.

4,235 citations