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ModBase, a database of annotated comparative protein structure models and associated resources

Pieper U, Webb BM, Dong GQ, Schneidman-Duhovny D, Fan H, Kim SJ, Khuri N, Spill YG, Weinkam P, Hammel M, Tainer JA, Nilges M, Sali A. (2014) Nucleic Acids Res. 42, D336-46. PMCID: PMC3965011

In a publication from the EFI Computation Core, the Sali Lab describes ModBase, an online database of annotated comparative protein structure models that provides the public with a resource for creating, analyzing, and comparing such models. ModBase and its embedded functionalities will prove to be invaluable as EFI researchers seek to assign functions to protein targets that lack high-resolution, experimentally-determined structures. 

ABSTRACT

ModBase is a database of annotated comparative protein structure models. The models are calculated by ModPipe, an automated modeling pipeline that relies primarily on Modeller for fold assignment, sequence-structure alignment, model building and model assessment. ModBase currently contains almost 30 million reliable models for domains in 4.7 million unique protein sequences. ModBase allows users to compute or update comparative models on demand, through an interface to the ModWeb modeling server. ModBase models are also available through the Protein Model Portal. Recently developed associated resources include the AllosMod server for modeling ligand-induced protein dynamics, the AllosMod-FoXS server for predicting a structural ensemble that fits an SAXS profile, the FoXSDock server for protein-protein docking filtered by an SAXS profile, the SAXS Merge server for automatic merging of SAXS profiles and the Pose & Rank server for scoring protein-ligand complexes. In this update, we also highlight two applications of ModBase: a PSI:Biology initiative to maximize the structural coverage of the human alpha-helical transmembrane proteome and a determination of structural determinants of human immunodeficiency virus-1 protease specificity.

Link to PubMed »

2014 Piper 01Figure 1. The computed profiles for filament models of the XLF–XRCC4 complex (63) are fitted to the experimental SAXS profile with FoXS. The interactive user interface displays the profiles in the left and the models in the right using the same color for each model/profile pair. The table below the panels displays the fit parameters and includes buttons to simultaneously show or hide each model/profile pair. Clicking on Minimal Ensemble Search (MES) results (above the display panel) takes the user to the MES output page.

2014 Piper 02Figure 2. Cleavage of human proteins by the HIV-1 protease: crystal structure of the N-terminal domain of human Lupus La protein (92) (left). Residues of the cleavage site (Ile-Asp-Tyr-Tyr-Phe-Gly-Glu-Phe) are shown in orange. Scissile bond between Tyr and Phe in the alpha-helix is cleaved by the HIV-1 protease in vitro.

2014 Piper 03Figure 3. ModBase interface elements. Search Form: search options are available through the pull-down menu. A quick overview of the available representations is displayed below the search form. Model Details Sketch: the Model details page provides information for all models of a given sequences. The sketch comprises two parts: the model coverage sketch that indicates the sequence coverage by all models (top line) and the sequence coverage by the current model (second line), and a ribbon diagram of the current model. Other models are available via thumbprints. Update and Remodel: this box shows the date of the last modeling calculation for the current sequence, and allows the user to request an update. Chimera Visualization: the visualization includes the model and template structures and the alignment. Cross-references: links to the PMP, UniProtKB, Genbank, UCSC Genome Browser and other databases. Model Details Options: the pull-down menu switches between representations and allows downloads of coordinate and alignment files. Quality Criteria: red indicates unreliable, green reliable. Model Overview: a different representation for several sequences gives a quick overview on modeling coverage and quality. Chimera Cavity View: visualizes cavities predicted by ConCavity.

Reprinted with permission from Oxford University Press. Copyright © 2014, Oxford University Press.