Topic
Phyre
About: Phyre is a research topic. Over the lifetime, 35 publications have been published within this topic receiving 11209 citations. The topic is also known as: Protein Homology/AnalogY Recognition Engine.
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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
TL;DR: This protocol provides a guide to interpreting the output of structure prediction servers in general and one such tool in particular, the protein homology/analogy recognition engine (Phyre), which can reliably detect up to twice as many remote homologies as standard sequence-profile searching.
Abstract: Determining the structure and function of a novel protein is a cornerstone of many aspects of modern biology. Over the past decades, a number of computational tools for structure prediction have been developed. It is critical that the biological community is aware of such tools and is able to interpret their results in an informed way. This protocol provides a guide to interpreting the output of structure prediction servers in general and one such tool in particular, the protein homology/analogy recognition engine (Phyre). New profile–profile matching algorithms have improved structure prediction considerably in recent years. Although the performance of Phyre is typical of many structure prediction systems using such algorithms, all these systems can reliably detect up to twice as many remote homologies as standard sequence-profile searching. Phyre is widely used by the biological community, with >150 submissions per day, and provides a simple interface to results. Phyre takes 30 min to predict the structure of a 250-residue protein.
4,403 citations
TL;DR: It is demonstrated how such ensembles of predictors can be designed in‐house under controlled conditions and permit significant improvements in recognition by using a concept taken from protein loop energetics and applying it to the general problem of 3D clustering.
Abstract: Structural and functional annotation of the large and growing database of genomic sequences is a major problem in modern biology. Protein structure prediction by detecting remote homology to known structures is a well-established and successful annotation technique. However, the broad spectrum of evolutionary change that accompanies the divergence of close homologues to become remote homologues cannot easily be captured with a single algorithm. Recent advances to tackle this problem have involved the use of multiple predictive algorithms available on the Internet. Here we demonstrate how such ensembles of predictors can be designed in-house under controlled conditions and permit significant improvements in recognition by using a concept taken from protein loop energetics and applying it to the general problem of 3D clustering. We have developed a stringent test that simulates the situation where a protein sequence of interest is submitted to multiple different algorithms and not one of these algorithms can make a confident (95%) correct assignment. A method of meta-server prediction (Phyre) that exploits the benefits of a controlled environment for the component methods was implemented. At 95% precision or higher, Phyre identified 64.0% of all correct homologous query-template relationships, and 84.0% of the individual test query proteins could be accurately annotated. In comparison to the improvement that the single best fold recognition algorithm (according to training) has over PSI-Blast, this represents a 29.6% increase in the number of correct homologous query-template relationships, and a 46.2% increase in the number of accurately annotated queries. It has been well recognised in fold prediction, other bioinformatics applications, and in many other areas, that ensemble predictions generally are superior in accuracy to any of the component individual methods. However there is a paucity of information as to why the ensemble methods are superior and indeed this has never been systematically addressed in fold recognition. Here we show that the source of ensemble power stems from noise reduction in filtering out false positive matches. The results indicate greater coverage of sequence space and improved model quality, which can consequently lead to a reduction in the experimental workload of structural genomics initiatives.
436 citations
Posted Content•
TL;DR: The PHYRE benchmark for physical reasoning is developed that contains a set of simple classical mechanics puzzles in a 2D physical environment to encourage the development of learning algorithms that are sample-efficient and generalize well across puzzles.
Abstract: Understanding and reasoning about physics is an important ability of intelligent agents. We develop the PHYRE benchmark for physical reasoning that contains a set of simple classical mechanics puzzles in a 2D physical environment. The benchmark is designed to encourage the development of learning algorithms that are sample-efficient and generalize well across puzzles. We test several modern learning algorithms on PHYRE and find that these algorithms fall short in solving the puzzles efficiently. We expect that PHYRE will encourage the development of novel sample-efficient agents that learn efficient but useful models of physics. For code and to play PHYRE for yourself, please visit this https URL.
55 citations
Proceedings Article•
15 Aug 2019TL;DR: The PHYRE benchmark as discussed by the authors is designed to encourage the development of learning algorithms that are sample-efficient and generalize well across puzzles in a 2D physical environment, and has been used to test several modern learning algorithms.
Abstract: Understanding and reasoning about physics is an important ability of intelligent agents. We develop the PHYRE benchmark for physical reasoning that contains a set of simple classical mechanics puzzles in a 2D physical environment. The benchmark is designed to encourage the development of learning algorithms that are sample-efficient and generalize well across puzzles. We test several modern learning algorithms on PHYRE and find that these algorithms fall short in solving the puzzles efficiently. We expect that PHYRE will encourage the development of novel sample-efficient agents that learn efficient but useful models of physics. For code and to play PHYRE for yourself, please visit https://player.phyre.ai.
55 citations