I-TASSER server for protein 3D structure prediction

Background: Prediction of 3-dimensional protein structures from amino acid sequences represents one of the most important problems in computational structural biology. The community-wide Critical Assessment of Structure Prediction (CASP) experiments have been designed to obtain an objective assessment of the state-of-the-art of the field, where I-TASSER was ranked as the best method in the server section of the recent 7th CASP experiment. Our laboratory has since then received numerous requests about the public availability of the I-TASSER algorithm and the usage of the I-TASSER predictions. Results: An on-line version of I-TASSER is developed at the KU Center for Bioinformatics which has generated protein structure predictions for thousands of modeling requests from more than 35 countries. A scoring function (C-score) based on the relative clustering structural density and the consensus significance score of multiple threading templates is introduced to estimate the accuracy of the I-TASSER predictions. A large-scale benchmark test demonstrates a strong correlation between the C-score and the TM-score (a structural similarity measurement with values in [0, 1]) of the first models with a correlation coefficient of 0.91. Using a C-score cutoff > -1.5 for the models of correct topology, both false positive and false negative rates are below 0.1. Combining C-score and protein length, the accuracy of the I-TASSER models can be predicted with an average error of 0.08 for TM-score and 2 Å for RMSD. Conclusion: The I-TASSER server has been developed to generate automated full-length 3D protein structural predictions where the benchmarked scoring system helps users to obtain quantitative assessments of the I-TASSER models. The output of the I-TASSER server for each query includes up to five full-length models, the confidence score, the estimated TM-score and RMSD, and the standard deviation of the estimations. The I-TASSER server is freely available to the academic community at http://zhang.bioinformatics.ku.edu/I-TASSER webcite

I-TASSER server for protein 3D structure prediction

<p>Abstract</p> <p>Background</p> <p>Prediction of 3-dimensional protein structures from amino acid sequences represents one of the most important problems in computational structural biology. The community-wide Critical Assessment of Structure Prediction (CASP) experiments have been designed to obtain an objective assessment of the state-of-the-art of the field, where I-TASSER was ranked as the best method in the server section of the recent 7th CASP experiment. Our laboratory has since then received numerous requests about the public availability of the I-TASSER algorithm and the usage of the I-TASSER predictions.</p> <p>Results</p> <p>An on-line version of I-TASSER is developed at the KU Center for Bioinformatics which has generated protein structure predictions for thousands of modeling requests from more than 35 countries. A scoring function (C-score) based on the relative clustering structural density and the consensus significance score of multiple threading templates is introduced to estimate the accuracy of the I-TASSER predictions. A large-scale benchmark test demonstrates a strong correlation between the C-score and the TM-score (a structural similarity measurement with values in [0, 1]) of the first models with a correlation coefficient of 0.91. Using a C-score cutoff > -1.5 for the models of correct topology, both false positive and false negative rates are below 0.1. Combining C-score and protein length, the accuracy of the I-TASSER models can be predicted with an average error of 0.08 for TM-score and 2 Å for RMSD.</p> <p>Conclusion</p> <p>The I-TASSER server has been developed to generate automated full-length 3D protein structural predictions where the benchmarked scoring system helps users to obtain quantitative assessments of the I-TASSER models. The output of the I-TASSER server for each query includes up to five full-length models, the confidence score, the estimated TM-score and RMSD, and the standard deviation of the estimations. The I-TASSER server is freely available to the academic community at <url>http://zhang.bioinformatics.ku.edu/I-TASSER</url>.</p

HotSpot Wizard 3.0: Automated design of site-specific mutations and smart libraries

HotSpot Wizard is an interactive web server for prediction of amino acid residues suitable for mutagenesis and construction of libraries of mutants with modified activity, specificity or stability [1]. Positions suitable for mutagenesis are evaluated based on protein structure using a combination of structural, functional and evolutionary information obtained from 7 internet databases and 22 computational tools [2]. The application was designed with an emphasis on an easy usage without the necessity of advanced knowledge of the studied system. This is the reason for the setting of all default values of the parameters based on the extensive analysis to appropriately represent a wide spectrum of input data. Four different strategies are automatically evaluated for every protein structure. Analysis of the results is being run directly in the web interface, which provides user-friendly visualization tool. Moreover, HotSpot Wizard provides a module for the design of a construction of protein mutant library with the support of an automatic detection of suitable target amino acids and corresponding degenerative codons. There are several new features for the version 3.0 to be released early 2018. Stability of single-point or multiple-point mutant can be predicted using the Rosetta scoring function [3]. Users can newly enter also protein sequence as the input for calculation. Then searching for structures or models in the databases of experimental structures or depositories of homology models is performed. The users can also run homology modelling using the programs Modeller [4] and I-Tasser [5]. The current version of the application is freely available for academic users at http://loschmidt.chemi.muni.cz/hotspotwizard. 1. Pavelka, A., Chovancova, E., Damborsky, J., 2009: HotSpot Wizard: a Web Server for Identification of Hot Spots in Protein Engineering. Nucleic Acids Research 37: W376-W383. 2. Bendl, J., Stourac, J., Sebestova, E., Vavra, O., Musil, M., Brezovsky, J., Damborsky, J., 2016: HotSpot Wizard 2: Automated Design of Site-Specific Mutations and Smart Libraries in Protein Engineering. Nucleic Acids Research 44: W479-W487. 3. Kellogg, E.H., Leaver-Fay, A., Baker, D., 2011: Role of Conformational Sampling in Computing Mutation-induced Changes in Protein Structure and Stability. Proteins 79: 830-838. 4. Sali, A., Blundell, T.L., 1993: Comparative Protein Modelling by Satisfaction of Spatial Restraints. Journal of Molecular Biology 234: 779-815. 5. Zhang, Y., 2008: I-TASSER Server for Protein 3D Structure Prediction. BMC Bioinformatics 9: 40

Study of the visual adaptation mechanism in marine species with the change of habitation depth.

The goal of our work was to determine the principal mechanisms that provide the difference in visual perception of two marine species that live on different depths: T. Pacificus and O. Vulgaris. In nature, visual perception of species that live deeper is shifted towards the blue region. This is related to the fact that red, orange and yellow light is absorbed more strongly by water than the blue light. On the other hand, the visual perception spectrum of an animal is determined by the absorption spectrum of the light sensor located in rods and cones of its eye retina. These light sensors are proteins from the rhodopsin family, which generate an electrical signal upon light absorption. Thus, in order to understand the mechanism of visual adaptation one has to study the molecular difference between the corresponding rhodopsins of the target species. We proposed new algorithms for exploring this molecular difference based on methodology from computational biophysics and quantum chemistry. These algorithms allowed us to predict the absorption maxima of visual proteins on the basis of their amino acid sequence. First, we tested these algorithms by predicting the absorption maxima of visual rhodopsins from several species. Second, we calculated the structures and absorption maxima of wild types and mutants of two rhodopsins of the target species. These calculations allowed us to determine the key mutation that is responsible for the spectral shift between two rhodopsins and determine the molecular mechanism of visual adaptation between two target marine species

PDBpaint, a visualization webservice to tag protein structures with sequence annotations

SUMMARY: Protein features are often displayed along the linear sequence of amino acids that make up that protein, but in reality these features occupy a position in the folded protein's three-dimensional space. Mapping sequence features to known or predicted protein structures is useful when trying to deduce the function of those features and when evaluating sequence or structural predictions. To facilitate this goal we developed PDBpaint, a simple tool that displays protein sequence features gathered from bioinformatics resources on top of protein structures, which are displayed in an interactive window (using the Jmol Java viewer). PDBpaint can be used either with existing protein structures or with novel structures provided by the user. The current version of PDBpaint allows the visualization of annotations from Pfam, ARD (detection of HEATrepeats), UniProt, TMHMM2.0 and SignalP. Users can also add other annotations manually. Availability and Implementation: PDBpaint is accessible at http://cbdm.mdc-berlin.de/~pdbpaint. Code is available from http://sourceforge.net/projects/pdbpaint. The website was implemented in Perl, with all major browsers supported. CONTACT: [email protected]

Isolation and Characterization of C-C Chemokine Ligand 7 (CCL7) in Cynomolgus Macaques

Cynomolgus macaques (Macaca fascicularis) are an established animal model of asthma, which exhibit different responses to allergen exposure that are clinically relevant. The chemokine ligand gene (CCL7) encodes Monocyte Chemotactic Protein-3, which has an important role in asthma pathogenesis. While CCL7 polymorphism in humans is associated with asthma phenotype, very little is known about CCL7 in nonhuman primate models of respiratory disease. The objective of this study was to isolate and characterize CCL7 gene in cynomolgus macaques of Indonesian origin. In this study, we used sequencing and bioinformatics technique for gene isolation, characterization, and protein 3D structure prediction. We isolated a 2253 base-pair (bp) sequence of CCL7 in cynomolgus macaques, which exhibited 95% similarity in coding sequence to human CCL7. The amino acid sequence was more closely clustered with human CCL7 than with that of rodents. Importantly, the predictive protein structure of CCL7 was similar to that in humans. These similarities in CCL7 suggests the potential of cynomolgus macaque as a translational model to study asthma, particularly in the context of genetics and role of chemokines such as CCL7

The use of structural modelling to infer structure and function in biocontrol agents

Homology modelling can provide important insights into the structures of proteins when a related protein structure has already been solved. However, for many proteins, including a number of invertebrate-active toxins and accessory proteins, no such templates exist. In these cases, techniques of ab initio, template-independent modelling can be employed to generate models that may give insight into structure and function. In this overview, examples of both the problems and the potential benefits of ab initio techniques are illustrated. Consistent modelling results may indicate useful approximations to actual protein structures and can thus allow the generation of hypotheses regarding activity that can be tested experimentally

СТРУКТУРНЫЕ ОСОБЕННОСТИ ЦИТОХРОМА P450 7B1 ЧЕЛОВЕКА С АМИНОКИСЛОТНОЙ ЗАМЕНОЙ Phe470Ile

To study the influence of the amino acid substitution of Phe470Ile, correlating with the spastic paraplegia of type 5, on the structure of human cytochrome P450 7B1, the spatial full-atomic models of this enzyme and its mutant form were created. It was found that Phe470 does not influence directly the catalytic properties of the enzyme because of its localization far from the active site. It was shown that the residue under investigation belongs to a highly conservative region of the protein structure and can influence the CYP7B1 correct folding. In particular, the amino acid substitution of Phe470Ile increases rigidity and stability of sterol 7α-hydroxylase. This can be a reason of changes in the CYP7B1 hydroxylase activity in relation to neurosteroids.С целью изучения влияния аминокислотной замены Phe470Ile, коррелирующей с возникновением спастической параплегии типа 5, на пространственную структуру цитохрома P450 7B1 человека построены компьютерные модели данного фермента и его варианта с соответствующей мутацией. Установлено, что Phe470 не влияет напрямую на каталитические свойства фермента в силу того, что он локализован далеко от активного центра фермента. Однако расположение 470 остатка в высоко консервативной области белка свидетельствует о его важной роли в формировании корректной пространственной структуры исследуемой стероид 7α-гидроксилазы. В частности, аминокислотная замена Phe470Ile приводит к увеличению жесткости и, как следствие этого, стабильности пространственной структуры CYP7B1, что может являться причиной изменения профиля гидроксилазной активности фермента по отношению к нейростероидам

THE BIOPHYSICAL CHARACTERISTICS AND STRUCTURAL EXPLORATION OF PROGRAMMED CELL DEATH REGULATOR B-CELL LYMPHOMA 2-ASSOCIATED X PROTEIN OF CHINESE LIVER FLUKE (CLONORCHIS SINENSIS)

 Objective: The balance between deaths and cellular life is regulated by B-cell lymphoma 2 (BCL-2)-associated X protein (BAX) an important pro-apoptotic components of BCL-2 family. With this initial point, the aim of this study was to determine a comparative composite based structure of BAX of Chinese liver fluke and different structural analysis.Methods: Protein amino acid of BAX of Chinese liver fluke mined from National Centre for Biotechnology Information (http://ncbi.nlm.nih.gov). Molecular model of BAX of Chinese liver fluke protein was generated by the comparative composite modeling tool Iterative Threading ASSEmbly Refinement suite. Afterward, I-TASSER generated molecular model was subjected to further structural improvements by energy minimization step. Distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, and hydrophobicity molecular surface analysis was performed with the help of bioinformatical tools.Results: Analysis of Ramachandran plot created by PROCHECK tool is a consensus standard for validation purpose of protein structural modeling. Altogether 97.8% of the residues were detected in allowed and favored regions, which in turn validate the quality of generated protein structural model. Total negatively and positively charged residues within the BAX of Chinese liver fluke were 23 and 20, respectively. Chimera package-guided hydrophobicity molecular surface analysis illustrates that molecule specific hydrophobicity surface is exclusive to BAX protein molecule.Conclusion: Within the scope of this scientific investigation, we have successfully utilized molecular modeling approach to suggest the first molecular three-dimensional model structure of BAX of Chinese liver fluke. The synchronous balance between cellular deaths and cellular life is keeping up by BAX, an important pro-apoptotic family member of BCL-2 family. Consequently, it would be an exciting approach to resolve its structural characterization and molecular structure to propose mode of mechanism action. Â