Article

Protein structure prediction: challenging targets for CASP10. (ITS FREE NOW.....)

Biological Sciences, Faculty Division III, Birla Institute of Technology & Science, Pilani, Rajasthan, India.
Journal of biomolecular Structure & Dynamics (Impact Factor: 2.98). 06/2012; 30(5):607-15. DOI: 10.1080/07391102.2012.687526
Source: PubMed

ABSTRACT Functional characterization of proteins being one of the major issues in molecular biology is still unsolved due to several resource and technical limitations of experimental structure determination methods. A suitable methodology for accurate prediction of protein confirmations simply from sequence is therefore emerging as the primary modeling goal of researchers today. Global blind protein structure prediction summit, entitled Critical Assessment of Structure Prediction (CASP), critically assesses the modeling methodologies, to track our algorithmic path development. But our success is still impeded by incompetent modeling methodologies and several key technical lacunas. There is still a great need to focus some key issues for bridging the major though considered trivial gaps, in the upcoming CASP to pave and demarcate our correct way of developing a consistently accurate prediction methodology in the near future. Major problems resulting in divergence of our predicted models from their actual native states are thus highlighted with suggested more stringent and reliable assessment considerations in the CASP test.

Link is ........http://www.tandfonline.com/doi/pdf/10.1080/07391102.2012.687526

1 Bookmark
 · 
302 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The ISA-Tab format and software suite have been developed to break the silo effect induced by technology-specific formats for a variety of data types and to better support experimental metadata tracking. Experimentalists seldom use a single technique to monitor biological signals. Providing a multi-purpose, pragmatic and accessible format that abstracts away common constructs for describing Investigations, Studies and Assays, ISA is increasingly popular. To attract further interest towards the format and extend support to ensure reproducible research and reusable data, we present the Risa package, which delivers a central component to support the ISA format by enabling effortless integration with R, the popular, open source data crunching environment. The Risa package bridges the gap between the metadata collection and curation in an ISA-compliant way and the data analysis using the widely used statistical computing environment R. The package offers functionality for: i) parsing ISA-Tab datasets into R objects, ii) augmenting annotation with extra metadata not explicitly stated in the ISA syntax; iii) interfacing with domain specific R packages iv) suggesting potentially useful R packages available in Bioconductor for subsequent processing of the experimental data described in the ISA format; and finally v) saving back to ISA-Tab files augmented with analysis specific metadata from R. We demonstrate these features by presenting use cases for mass spectrometry data and DNA microarray data. The Risa package is open source (with LGPL license) and freely available through Bioconductor. By making Risa available, we aim to facilitate the task of processing experimental data, encouraging a uniform representation of experimental information and results while delivering tools for ensuring traceability and provenance tracking. The Risa package is available since Bioconductor 2.11 (version 1.0.0) and version 1.2.1 appeared in Bioconductor 2.12, both along with documentation and examples. The latest version of the code is at the development branch in Bioconductor and can also be accessed from GitHub https://github.com/ISA-tools/Risa, where the issue tracker allows users to report bugs or feature requests.
    BMC Bioinformatics 01/2014; 15 Suppl 1:S11. · 3.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The expansion of polyglutamine (poly-Q) repeats in several unrelated proteins is associated with at least ten neurodegenerative diseases. The length of the poly-Q regions plays an important role in the progression of the diseases. The number of glutamines (Q) is inversely related to the onset age of these polyglutamine diseases, and the expansion of poly-Q repeats has been associated with protein misfolding. However, very little is known about the structural changes induced by the expansion of the repeats. Computational methods can provide an alternative to determine the structure of these poly-Q proteins, but it is important to evaluate their performance before large scale prediction work is done.
    BMC Bioinformatics 05/2014; 15(Suppl 7):S11. · 3.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Within the idiosyncratic enzyme active-site environment, side chain and ligand pKa values can be profoundly perturbed relative to their values in aqueous solution. Whereas structural inspection of systems has often attributed perturbed pKa values to dominant contributions from placement near charged groups or within hydrophobic pockets, Tyr57 of a Pseudomonas putida ketosteroid isomerase (KSI) mutant, suggested to have a pKa perturbed by nearly 4 units to 6.3, is situated within a solvent-exposed active site devoid of cationic side chains, metal ions, or cofactors. Extensive comparisons among 45 variants with mutations in and around the KSI active site, along with protein semisynthesis, (13)C NMR spectroscopy, absorbance spectroscopy, and X-ray crystallography, was used to unravel the basis for this perturbed Tyr pKa. The results suggest that the origin of large energetic perturbations are more complex than suggested by visual inspection. For example, the introduction of positively charged residues near Tyr57 raises its pKa rather than lowers it; this effect, and part of the increase in the Tyr pKa from the introduction of nearby anionic groups, arises from accompanying active-site structural rearrangements. Other mutations with large effects also cause structural perturbations or appear to displace a structured water molecule that is part of a stabilizing hydrogen-bond network. Our results lead to a model in which three hydrogen bonds are donated to the stabilized ionized Tyr, with these hydrogen-bond donors, two Tyr side chains, and a water molecule positioned by other side chains and by a water-mediated hydrogen-bond network. These results support the notion that large energetic effects are often the consequence of multiple stabilizing interactions rather than a single dominant interaction. Most generally, this work provides a case study for how extensive and comprehensive comparisons via site-directed mutagenesis in a tight feedback loop with structural analysis can greatly facilitate our understanding of enzyme active-site energetics. The extensive data set provided may also be a valuable resource for those wishing to extensively test computational approaches for determining enzymatic pKa values and energetic effects.
    Biochemistry 10/2013; · 3.38 Impact Factor