Predicting protein function from sequence and structural data

Watson, James D.; Laskowski, Roman A.; Thornton, Janet M.

doi:10.1016/j.sbi.2005.04.003

Cited by 280 publications

(219 citation statements)

References 68 publications

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“…The more similar the sequence is, the more similar the function of the proteins. Having 100% sequence identity yet preforming different roles according to their expression in different cellular and nuclear regions [64,65] is biologically important for disease pathogenesis. The FASTA amino acid sequence of UBE2D4 was retrieved from the ExPASy/UniProt proteomics server (http://www.uniprot.org/).…”

Section: Ube2d4 Protein Modelling and Validationmentioning

confidence: 99%

Targeting the ubiquitin-conjugating enzyme E2D4 for cancer drug discovery–a structure-based approach

et al. 2016

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Cancer progression is a global burden. The incidence and mortality now reach 30 million deaths per year. Several pathways of cancer are under investigation for the discovery of effective therapeutics. The present study highlights the structural details of the ubiquitin protein 'Ubiquitin-conjugating enzyme E2D4' (UBE2D4) for the novel lead structure identification in cancer drug discovery process. The evaluation of 3D structure of UBE2D4 was carried out using homology modelling techniques. The optimized structure was validated by standard computational protocols. The active site region of the UBE2D4 was identified using computational tools like CASTp, Q-site Finder and SiteMap. The hydrophobic pocket which is responsible for binding with its natural receptor ubiquitin ligase CHIP (C-terminal of Hsp 70 interacting protein) was identified through proteinprotein docking study. Corroborating the results obtained from active site prediction tools and protein-protein docking study, the domain of UBE2D4 which is responsible for cancer cell progression is sorted out for further docking study. Virtual screening with large structural database like CB_Div Set and Asinex BioDesign small molecular structural database was carried out. The obtained new ligand molecules that have shown affinity towards UBE2D4 were considered for ADME prediction studies. The identified new ligand molecules with acceptable parameters of docking, ADME are considered as potent UBE2D4 enzyme inhibitors for cancer therapy.

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Section: Ube2d4 Protein Modelling and Validationmentioning

confidence: 99%

Targeting the ubiquitin-conjugating enzyme E2D4 for cancer drug discovery–a structure-based approach

et al. 2016

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“…Case studies on biologically important motifs Novel high-throughput experimental techniques produce a large amount of data on the 3D structure of proteins and their structural motifs. These motifs can be used as patterns in drug discovery [1], can help to understand the relationship between a protein's structure and its function [2] and to classify proteins [3]. In order to extract as much information as possible from this data, new techniques and tools are necessary, and among them fast approaches to perform the multiple superimposition of large sets of protein structural motifs.…”

Section: P O S T E R P R E S E N T a T I O N Open Accessmentioning

confidence: 99%

SiteBinder: An Improved Approach for Comparing Multiple Protein Structural Motifs

Sehnal

Vařeková

Huber

et al. 2012

J. Chem. Inf. Model.

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There is a paramount need to develop new techniques and tools that will extract as much information as possible from the ever growing repository of protein 3D structures. We report here on the development of a software tool for the multiple superimposition of large sets of protein structural motifs. Our superimposition methodology performs a systematic search for the atom pairing that provides the best fit. During this search, the RMSD values for all chemically relevant pairings are calculated by quaternion algebra. The number of evaluated pairings is markedly decreased by using PDB annotations for atoms. This approach guarantees that the best fit will be found and can be applied even when sequence similarity is low or does not exist at all. We have implemented this methodology in the Web application SiteBinder, which is able to process up to thousands of protein structural motifs in a very short time, and which provides an intuitive and user-friendly interface. Our benchmarking analysis has shown the robustness, efficiency, and versatility of our methodology and its implementation by the successful superimposition of 1000 experimentally determined structures for each of 32 eukaryotic linear motifs. We also demonstrate the applicability of SiteBinder using three case studies. We first compared the structures of 61 PA-IIL sugar binding sites containing nine different sugars, and we found that the sugar binding sites of PA-IIL and its mutants have a conserved structure despite their binding different sugars. We then superimposed over 300 zinc finger central motifs and revealed that the molecular structure in the vicinity of the Zn atom is highly conserved. Finally, we superimposed 12 BH3 domains from pro-apoptotic proteins. Our findings come to support the hypothesis that there is a structural basis for the functional segregation of BH3-only proteins into activators and enablers.

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“…CPASS is a structure-based functional annotation program that differs from a variety of 3D template or sequence-based annotation programs (for a review see Watson et al (2005) [50]) routinely used to predict ligand binding sites and protein function. These programs attempt to predict the location of ligand binding sites using various sequence and structure heuristics.…”

Section: Cpassmentioning

confidence: 99%

The application of FAST-NMR for the identification of novel drug discovery targets

Powers

Mercier

Copeland

2008

Drug Discovery Today

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Predicting protein function from sequence and structural data

Cited by 280 publications

References 68 publications

Targeting the ubiquitin-conjugating enzyme E2D4 for cancer drug discovery–a structure-based approach

Targeting the ubiquitin-conjugating enzyme E2D4 for cancer drug discovery–a structure-based approach

SiteBinder: An Improved Approach for Comparing Multiple Protein Structural Motifs

The application of FAST-NMR for the identification of novel drug discovery targets

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