Dataset Information

XLinkDB 2.0: integrated, large-scale structural analysis of protein crosslinking data.

ABSTRACT:

Motivation

Large-scale chemical cross-linking with mass spectrometry (XL-MS) analyses are quickly becoming a powerful means for high-throughput determination of protein structural information and protein-protein interactions. Recent studies have garnered thousands of cross-linked interactions, yet the field lacks an effective tool to compile experimental data or access the network and structural knowledge for these large scale analyses. We present XLinkDB 2.0 which integrates tools for network analysis, Protein Databank queries, modeling of predicted protein structures and modeling of docked protein structures. The novel, integrated approach of XLinkDB 2.0 enables the holistic analysis of XL-MS protein interaction data without limitation to the cross-linker or analytical system used for the analysis.

Availability and implementation

XLinkDB 2.0 can be found here, including documentation and help: http://xlinkdb.gs.washington.edu/

Contact

: jimbruce@uw.edu

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Schweppe DK

PROVIDER: S-EPMC5013903 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

XLinkDB 2.0: integrated, large-scale structural analysis of protein crosslinking data.

Schweppe Devin K DK Zheng Chunxiang C Chavez Juan D JD Navare Arti T AT Wu Xia X Eng Jimmy K JK Bruce James E JE

Bioinformatics (Oxford, England) 20160429 17

<h4>Motivation</h4>Large-scale chemical cross-linking with mass spectrometry (XL-MS) analyses are quickly becoming a powerful means for high-throughput determination of protein structural information and protein-protein interactions. Recent studies have garnered thousands of cross-linked interactions, yet the field lacks an effective tool to compile experimental data or access the network and structural knowledge for these large scale analyses. We present XLinkDB 2.0 which integrates tools for n ...[more]

PMID: 27153666

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Project description:BackgroundLarge-scale datasets of protein structures and sequences are becoming ubiquitous in many domains of biological research. Experimental approaches and computational modelling methods are generating biological data at an unprecedented rate. The detailed analysis of structure-sequence relationships is critical to unveil governing principles of protein folding, stability and function. Computational protein design (CPD) has emerged as an important structure-based approach to engineer proteins for novel functions. Generally, CPD workflows rely on the generation of large numbers of structural models to search for the optimal structure-sequence configurations. As such, an important step of the CPD process is the selection of a small subset of sequences to be experimentally characterized. Given the limitations of current CPD scoring functions, multi-step design protocols and elaborated analysis of the decoy populations have become essential for the selection of sequences for experimental characterization and the success of CPD strategies.ResultsHere, we present the rstoolbox, a Python library for the analysis of large-scale structural data tailored for CPD applications. rstoolbox is oriented towards both CPD software users and developers, being easily integrated in analysis workflows. For users, it offers the ability to profile and select decoy sets, which may guide multi-step design protocols or for follow-up experimental characterization. rstoolbox provides intuitive solutions for the visualization of large sequence/structure datasets (e.g. logo plots and heatmaps) and facilitates the analysis of experimental data obtained through traditional biochemical techniques (e.g. circular dichroism and surface plasmon resonance) and high-throughput sequencing. For CPD software developers, it provides a framework to easily benchmark and compare different CPD approaches. Here, we showcase the rstoolbox in both types of applications.Conclusionsrstoolbox is a library for the evaluation of protein structures datasets tailored for CPD data. It provides interactive access through seamless integration with IPython, while still being suitable for high-performance computing. In addition to its functionalities for data analysis and graphical representation, the inclusion of rstoolbox in protein design pipelines will allow to easily standardize the selection of design candidates, as well as, to improve the overall reproducibility and robustness of CPD selection processes.

Project description:BACKGROUND: Large-scale protein interaction maps provide a new, global perspective with which to analyse protein function. PSIMAP, the Protein Structural Interactome Map, is a database of all the structurally observed interactions between superfamilies of protein domains with known three-dimensional structure in the PDB. PSIMAP incorporates both functional and evolutionary information into a single network. RESULTS: We present a global analysis of PSIMAP using several distinct network measures relating to centrality, interactivity, fault-tolerance, and taxonomic diversity. We found the following results: Centrality: we show that the center and barycenter of PSIMAP do not coincide, and that the superfamilies forming the barycenter relate to very general functions, while those constituting the center relate to enzymatic activity. Interactivity: we identify the P-loop and immunoglobulin superfamilies as the most highly interactive. We successfully use connectivity and cluster index, which characterise the connectivity of a superfamily's neighbourhood, to discover superfamilies of complex I and II. This is particularly significant as the structure of complex I is not yet solved. Taxonomic diversity: we found that highly interactive superfamilies are in general taxonomically very diverse and are thus amongst the oldest. Fault-tolerance: we found that the network is very robust as for the majority of superfamilies removal from the network will not break up the network. CONCLUSIONS: Overall, we can single out the P-loop containing nucleotide triphosphate hydrolases superfamily as it is the most highly connected and has the highest taxonomic diversity. In addition, this superfamily has the highest interaction rank, is the barycenter of the network (it has the shortest average path to every other superfamily in the network), and is an articulation vertex, whose removal will disconnect the network. More generally, we conclude that the graph-theoretic and taxonomic analysis of PSIMAP is an important step towards the understanding of protein function and could be an important tool for tracing the evolution of life at the molecular level.

Dataset Information

XLinkDB 2.0: integrated, large-scale structural analysis of protein crosslinking data.

Motivation

Availability and implementation

Contact

Supplementary information

Publications

XLinkDB 2.0: integrated, large-scale structural analysis of protein crosslinking data.

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