MODE-TASK: Large-scale protein motion tools
- Ross, Caroline J, Nizami, B, Glenister, Michael, Amamuddy, Olivier S, Atilgan, Ali R, Atilgan, Canan, Tastan Bishop, Özlem
- Authors: Ross, Caroline J , Nizami, B , Glenister, Michael , Amamuddy, Olivier S , Atilgan, Ali R , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125206 , vital:35746 , http://dx.doi.org/10.1101/217505
- Description: Conventional analysis of molecular dynamics (MD) trajectories may not identify global motions of macromolecules. Normal Mode Analysis (NMA) and Principle Component Analysis (PCA) are two popular methods to quantify large-scale motions, and find the “essential motions”; and have been applied to problems such as drug resistant mutations (Nizami et al., 2016) and viral capsid expansion (Hsieh et al., 2016). MODE-TASK is an array of tools to analyse and compare protein dynamics obtained from MD simulations and/or coarse grained elastic network models. Users may perform standard PCA, kernel and incremental PCA (IPCA). Data reduction techniques (Multidimensional Scaling (MDS) and t-Distributed Stochastics Neighbor Embedding (t-SNE)) are implemented. Users may analyse normal modes by constructing elastic network models (ENMs) of a protein complex. A novel coarse graining approach extends its application to large biological assemblies.
- Full Text:
- Date Issued: 2018
- Authors: Ross, Caroline J , Nizami, B , Glenister, Michael , Amamuddy, Olivier S , Atilgan, Ali R , Atilgan, Canan , Tastan Bishop, Özlem
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125206 , vital:35746 , http://dx.doi.org/10.1101/217505
- Description: Conventional analysis of molecular dynamics (MD) trajectories may not identify global motions of macromolecules. Normal Mode Analysis (NMA) and Principle Component Analysis (PCA) are two popular methods to quantify large-scale motions, and find the “essential motions”; and have been applied to problems such as drug resistant mutations (Nizami et al., 2016) and viral capsid expansion (Hsieh et al., 2016). MODE-TASK is an array of tools to analyse and compare protein dynamics obtained from MD simulations and/or coarse grained elastic network models. Users may perform standard PCA, kernel and incremental PCA (IPCA). Data reduction techniques (Multidimensional Scaling (MDS) and t-Distributed Stochastics Neighbor Embedding (t-SNE)) are implemented. Users may analyse normal modes by constructing elastic network models (ENMs) of a protein complex. A novel coarse graining approach extends its application to large biological assemblies.
- Full Text:
- Date Issued: 2018
The generation and characterisation of neutralising antibodies against the Theiler’s murine encephalomyelitis virus (TMEV) GDVII capsid reveals the potential binding site of the host cell co-receptor, heparan sulfate:
- Upfold, Nicole, Ross, Caroline J, Tastan Bishop, Özlem, Luke, Garry A, Knox, Caroline M
- Authors: Upfold, Nicole , Ross, Caroline J , Tastan Bishop, Özlem , Luke, Garry A , Knox, Caroline M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148181 , vital:38717 , DOI: 10.1016/j.virusres.2017.11.017
- Description: The early stages of picornavirus capsid assembly and the host factors involved are poorly understood. Since the localisation of viral proteins in infected cells can provide information on their function, antibodies against purified Theiler's murine encephalomyelitis virus (TMEV) GDVII capsids were generated by immunisation of rabbits. The resultant anti-TMEV capsid antibodies recognised a C-terminal region of VP1 but not VP2 or VP3 by Western analysis. Examination of the sites of TMEV capsid assembly by indirect immunofluorescence and confocal microscopy showed that at 5 h post infection, capsid signal was diffusely cytoplasmic with strong perinuclear staining and moved into large punctate structures from 6 to 8 h post infection.
- Full Text:
- Date Issued: 2018
- Authors: Upfold, Nicole , Ross, Caroline J , Tastan Bishop, Özlem , Luke, Garry A , Knox, Caroline M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148181 , vital:38717 , DOI: 10.1016/j.virusres.2017.11.017
- Description: The early stages of picornavirus capsid assembly and the host factors involved are poorly understood. Since the localisation of viral proteins in infected cells can provide information on their function, antibodies against purified Theiler's murine encephalomyelitis virus (TMEV) GDVII capsids were generated by immunisation of rabbits. The resultant anti-TMEV capsid antibodies recognised a C-terminal region of VP1 but not VP2 or VP3 by Western analysis. Examination of the sites of TMEV capsid assembly by indirect immunofluorescence and confocal microscopy showed that at 5 h post infection, capsid signal was diffusely cytoplasmic with strong perinuclear staining and moved into large punctate structures from 6 to 8 h post infection.
- Full Text:
- Date Issued: 2018
Unraveling the Motions behind Enterovirus 71 Uncoating:
- Ross, Caroline J, Atilgan, Ali R, Tastan Bishop, Özlem, Atilgan, Canan
- Authors: Ross, Caroline J , Atilgan, Ali R , Tastan Bishop, Özlem , Atilgan, Canan
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148158 , vital:38715 , DOI: 10.1016/j.bpj.2017.12.021
- Description: Enterovirus 71 can be a severe pathogen in small children and immunocompromised adults. Virus uncoating is a critical step in the infection of the host cell; however, the mechanisms that control this process remain poorly understood. We applied normal mode analysis and perturbation response scanning to several complexes of the virus capsid and present a coarse-graining approach to analyze the full capsid. We show that our method offers an alternative to expressing the system as a set of rigid blocks and accounts for the interconnection between nodes within each subunit and protein interfaces across the capsid. In our coarse-grained approach, the modes associated with capsid expansion are captured in the first three nondegenerate modes and correspond to the changes observed in structural studies of the virus. We show that the resolution of the analysis may be modified without losing information on the global motions leading to uncoating.
- Full Text:
- Date Issued: 2018
- Authors: Ross, Caroline J , Atilgan, Ali R , Tastan Bishop, Özlem , Atilgan, Canan
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148158 , vital:38715 , DOI: 10.1016/j.bpj.2017.12.021
- Description: Enterovirus 71 can be a severe pathogen in small children and immunocompromised adults. Virus uncoating is a critical step in the infection of the host cell; however, the mechanisms that control this process remain poorly understood. We applied normal mode analysis and perturbation response scanning to several complexes of the virus capsid and present a coarse-graining approach to analyze the full capsid. We show that our method offers an alternative to expressing the system as a set of rigid blocks and accounts for the interconnection between nodes within each subunit and protein interfaces across the capsid. In our coarse-grained approach, the modes associated with capsid expansion are captured in the first three nondegenerate modes and correspond to the changes observed in structural studies of the virus. We show that the resolution of the analysis may be modified without losing information on the global motions leading to uncoating.
- Full Text:
- Date Issued: 2018
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