Challenging the state of the art in protein structure prediction: Highlights of experimental target structures for the 10th Critical Assessment of Techniques for Protein Structure Prediction Experiment CASP10

Abstract

For the last two decades, CASP has assessed the state of the art in techniques for protein structure prediction and identified areas which required further development. CASP would not have been possible without the prediction targets provided by the experimental structural biology community. In the latest experiment, CASP10, over 100 structures were suggested as prediction targets, some of which appeared to be extraordinarily difficult for modeling. In this paper, authors of some of the most challenging targets discuss which specific scientific question motivated the experimental structure determination of the target protein, which structural features were especially interesting from a structural or functional perspective, and to what extent these features were correctly reproduced in the predictions submitted to CASP10. Specifically, the following targets will be presented: the acid-gated urea channel, a difficult to predict trans-membrane protein from the important human pathogen Helicobacter pylori; the structure of human interleukin IL-34, a recently discovered helical cytokine; the structure of a functionally uncharacterized enzyme OrfY from Thermoproteus tenax formed by a gene duplication and a novel fold; an ORFan domain of mimivirus sulfhydryl oxidase R596; the fibre protein gp17 from bacteriophage T7; the Bacteriophage CBA-120 tailspike protein; a virus coat protein from metagenomic samples of the marine environment; and finally an unprecedented class of structure prediction targets based on engineered disulfide-rich small proteins.

Structural modeling and analysis of dengue-mediated inhibition of interferon signaling pathway

“…They can be correlated with a structure determined with a medium resolution nuclear magnetic resonance (NMR), which needs nearly 50% identity of the sequence of the query to its template (Baker and Sali, 2001). Homology modeling of biological entities is a more efficient, accurate, and reliable method than other experimental methods (Kryshtafovych et al, 2014). The sequence of STAT2 had 44% sequence identity with 63% positives and 2 gaps, when compared with the sequence of the crystal structure of its template structure of STAT1, indicating that the homology model of STAT2 utilized in this study produced noteworthy and insightful results.…”

Crowdsourcing biomedical research: leveraging communities as innovation engines

“…Among the researcher-driven Challenges, the areas that have most profited are: structural biology (Critical Assessment of protein Structure Prediction (CASP) 18 and Critical Assessment of PRediction of Interaction (CAPRI) 19 ); genomics (Sequence Squeeze, Assemblathon and Critical Assessment of Massive Data Analysis (CAMDA)); systems biology (Systems Biology Verification combined with Industrial Methodology for Process Verification in Research (sbv-IMPROVER) and Critical Assessment of Genome Interpretation (CAGI)); text mining (BioCreative 20 , Cross-language Access to Catalogues And On-line libraries (CACAO) and Text REtrieval Conference Crowdsourcing Track (TREC Crowd)); curation and annotation (Critical Assessment of Functional Annotation (CAFA)); medicine (Children’s Leadership Award for the Reliable Interpretation and appropriate Transmission of Your genomic information (CLARITY) and Medical Image Computing and Computer Assisted Intervention (MICCAI)); and emerging technologies in search of benchmarking and new analytical tools (Flow Cytometry Critical Assessment of Population Identification Methods (FlowCAP) 21 ). Challenges also provide a framework to evaluate the ability of software pipelines to process different data types, such as the RNA-seq Genome Annotation Assessment Project (RGASP), which runs a competition to evaluate the software to align partial transcript reads to a reference genome sequence, which is a key step in RNA sequencing (RNAseq) data processing 22,23 .…”

Advances in GPCR Modeling Evaluated by the GPCR Dock 2013 Assessment: Meeting New Challenges

“…While of similar philosophy and organization to CASP and CAPRI assessments (Kryshtafovych et al, 2014; Lensink and Wodak, 2010; Moult et al, 2014), GPCR Dock focuses on specifics of GPCR-ligand complexes as opposed to the wider structural proteome dominated by soluble and globular proteins. It thus addresses a different set of challenges including distinct intramolecular packing principles influenced by the native lipid environment of GPCRs, a dynamic conformational equilibrium, evolutionally and conformationally variable loops, all of which ultimately affect ligand binding and function.…”