Bhageerath-H: A homology/ab initio hybrid server for predicting tertiary structures of monomeric soluble proteins

Jayaram, B.; Dhingra, Priyanka; Mishra, Avinash; Kaushik, Rahul; Mukherjee, Goutam; Singh, Ankita; Shekhar, Shashank

doi:10.1186/1471-2105-15-s16-s7

Cited by 54 publications

(26 citation statements)

References 102 publications

(73 reference statements)

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“…7A to C). The simulations were carried out with a tertiary structure for VP4 predicted by Bhageerath-H (22)(23)(24)(25)(26). Of the five predicted possible structures, the lowest-energy structure, comprised of a helix-turn-helix conformation, was selected as the Liposomes mimicking late endosomal vesicles were tested at two pH conditions, 7.0 and 5.5.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The VP4 Peptide of Hepatitis A Virus Ruptures Membranes through Formation of Discrete Pores

Shukla

Padhi

Gomes

et al. 2014

J Virol

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Membrane-active peptides, components of capsid structural proteins, assist viruses in overcoming the host membrane barrier in the initial stages of infection. Several such peptides have been identified, and their roles in membrane fusion or disruption have been characterized through biophysical studies. In several members of the Picornaviridae family, the role of the VP4 structural peptide in cellular-membrane penetration is well established. However, there is not much information on the membrane-penetrating capsid components of hepatitis A virus (HAV), an unusual member of this family. The VP4 peptide of HAV differs from its analogues in other picornaviruses in being significantly shorter in length and in lacking a signal for myristoylation, thought to be a critical requisite for VP4-mediated membrane penetration. Here we report, for the first time, that the atypical VP4 in HAV contains significant membrane-penetrating activity. Using a combination of biophysical assays and molecular dynamics simulation studies, we show that VP4 integrates into membrane vesicles through its N-terminal region to finally form discrete pores of 5-to 9-nm diameter, which induces leakage in the vesicles without altering their overall size or shape. We further demonstrate that the membrane activity of VP4 is specific toward vesicles mimicking the lipid content of late endosomes at acidic pH. Taken together, our data indicate that VP4 might be essential for the penetration of host endosomal membranes and release of the viral genome during HAV entry. IMPORTANCEHepatitis A virus causes acute hepatitis in humans through the fecal-oral route and is particularly prevalent in underdeveloped regions with poor hygienic conditions. Although a vaccine for HAV exists, its high cost makes it unsuitable for universal application in developing countries. Studies on host-virus interaction for HAV have been hampered due to a lack of starting material, since the virus is extremely slow growing in culture. Among the unknown aspects of the HAV life cycle is its manner of host membrane penetration, which is one of the most important initial steps in viral infection. Here, we present data to suggest that a small peptide, VP4, a component of the HAV structural polyprotein, might be essential in helping the viral genome cross cell membranes during entry. It is hoped that this work might help in elucidating the manner of initial host cell interaction by HAV.

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Section: Resultsmentioning

confidence: 99%

“…The three-dimensional structure of HAV VP4 ( 1 MNMSRQGIFQT-VGSGLDHILSLA 23 ) was predicted using Bhageerath-H (a homology ab initio hybrid web server for protein tertiary structure prediction) (22)(23)(24)(25)(26). Of the five candidate predicted structures (see Fig.…”

Section: Molecular Dynamics Simulation (I) Structure Prediction Of Hmentioning

confidence: 99%

The VP4 Peptide of Hepatitis A Virus Ruptures Membranes through Formation of Discrete Pores

Shukla

Padhi

Gomes

et al. 2014

J Virol

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“…Several web servers based on this theory are available which are ranked by a CASP assessment [53]. We have used two online servers, viz., Bhageerath [54] and Robetta [55] to model the 3D structures of our query protein. These two servers have been ranked amongst the top 20 from the recent CASP11 assessment in 2016 [56].…”

Section: Model Prediction Of Hops2mentioning

confidence: 99%

Identification and analysis of structurally critical fragments in HopS2

Borah

Jha

2019

BMC Bioinformatics

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Background: Among the diverse roles of the Type III secretion-system (T3SS), one of the notable functions is that it serves as unique nano machineries in gram-negative bacteria that facilitate the translocation of effector proteins from bacteria into their host. These effector proteins serve as potential targets to control the pathogenicity conferred to the bacteria. Despite being ideal choices to disrupt bacterial systems, it has been quite an ordeal in the recent times to experimentally reveal and establish a concrete sequence-structure-function relationship for these effector proteins. This work focuses on the disease-causing spectrum of an effector protein, HopS2 secreted by the phytopathogen Pseudomonas syringae pv. tomato DC3000. Results:The study addresses the structural attributes of HopS2 via a bioinformatics approach to by-pass some of the experimental shortcomings resulting in mining some critical regions in the effector protein. We have elucidated the functionally important regions of HopS2 with the assistance of sequence and structural analyses. The sequence based data supports the presence of important regions in HopS2 that are present in the other functional parts of Hop family proteins. Furthermore, these regions have been validated by an ab-initio structure prediction of the protein followed by 100 ns long molecular dynamics (MD) simulation. The assessment of these secondary structural regions has revealed the stability and importance of these regions in the protein structure. Conclusions: The analysis has provided insights on important functional regions that may be vital to the effector functioning. In dearth of ample experimental evidence, such a bioinformatics approach has helped in the revelation of a few structural regions which will aid in future experiments to attain and evaluate the structural and functional aspects of this protein family.

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“…Figure 2 provides an example of the tertiary structure of the Protective Antigen protein (UniProt ID: P13423). Aside from secondary structure prediction, prediction for this level structure normally falls on homology modeling method [21]. The homology modeling is also known as comparative modeling, in which the main result candidate comes from the amino acid sequence alignment by mapping the amino acid between different sequences.…”

Section: A Structural Informationmentioning

confidence: 99%

Towards Elucidating the Structural Principles of Host-Pathogen Protein-Protein Interaction Networks: A Bioinformatics Survey

Chen

Song

Sun

et al. 2017

2017 IEEE International Congress on Big Data (BigData Congress)

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The ultimate goal of systems biology research area is to accurately predict the behavior of biological systems through the construction of computational models, using the related molecular-level data as the input, especially when the structural information of such biological system is available. Combining the three-dimensional (3D) structural information of the cohort of macromolecules underpinning the biological system, the researchers are poised with an unprecedented opportunity to gain a full understanding on how the molecules interact with each other, particularly for an interaction network, e.g. protein-protein interaction networks. Specifically, there are currently a limited number of studies focused on the reconstruction and modelling of the structural interaction networks (SIN) between hostspathogens protein-protein interaction networks. In this paper, we will survey the SIN on protein-protein interactions network, in which we focus on the interactions between pathogen and host species (PHPPI). As one of the most important component of inter-species PPI study, in-depth study of PHPPI at atomicresolution level would reveal novel insights into the underlying principles of the organization and complexity of host-pathogen PPI networks. Several related sub areas are discussed, and the related typical Big Data methods including machine learning methodologies and statistics models will also be discussed. This paper contributes to a new, yet challenging, research area in applying data analytic and machine learning technologies in bioinformatics.Abstract-The ultimate goal of systems biology research area is to accurately predict the behavior of biological systems through the construction of computational models, using the related molecular-level data as the input, especially when the structural information of such biological system is available. Combining the three-dimensional (3D) structural information of the cohort of macromolecules underpinning the biological system, the researchers are poised with an unprecedented opportunity to gain a full understanding on how the molecules interact with each other, particularly for an interaction network, e.g. protein-protein interaction networks. Specifically, there are currently a limited number of studies focused on the reconstruction and modelling of the structural interaction networks (SIN) between hosts-pathogens protein-protein interaction networks. In this paper, we will survey the SIN on protein-protein interactions network, in which we focus on the interactions between pathogen and host species (PHPPI). As one of the most important component of inter-species PPI study, in-depth study of PHPPI at atomic-resolution level would reveal novel insights into the underlying principles of the organization and complexity of host-pathogen PPI networks. Several related sub areas are discussed, and the related typical Big Data methods including machine learning methodologies and statistics models will also be discussed. This paper contributes to a new, yet challenging, researc...

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Bhageerath-H: A homology/ab initio hybrid server for predicting tertiary structures of monomeric soluble proteins

Cited by 54 publications

References 102 publications

The VP4 Peptide of Hepatitis A Virus Ruptures Membranes through Formation of Discrete Pores

The VP4 Peptide of Hepatitis A Virus Ruptures Membranes through Formation of Discrete Pores

Identification and analysis of structurally critical fragments in HopS2

Towards Elucidating the Structural Principles of Host-Pathogen Protein-Protein Interaction Networks: A Bioinformatics Survey

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