Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs [version 1; peer review: 2 approved]

Background: Mycobacterial α-crystallin (Acr) is a chaperone that prevents misfolding of proteins when Mycobacterium tuberculosis is found in a latent form in the host tissue. Methods: Using insulin as a model substrate and utilizing polynomial graphs, we attempted to predict molecular-level interact...

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Main Authors: Gautam Krishnan, Utpal Roy
Format: Article
Language:English
Published: F1000 Research Ltd 2018-11-01
Series:F1000Research
Online Access:https://f1000research.com/articles/7-1801/v1
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author Gautam Krishnan
Utpal Roy
author_facet Gautam Krishnan
Utpal Roy
author_sort Gautam Krishnan
collection DOAJ
description Background: Mycobacterial α-crystallin (Acr) is a chaperone that prevents misfolding of proteins when Mycobacterium tuberculosis is found in a latent form in the host tissue. Methods: Using insulin as a model substrate and utilizing polynomial graphs, we attempted to predict molecular-level interactions that are a function of the oligomeric state of the recombinant protein. The chaperone activity of the recombinant oligomeric Acr was measured at 60°C with Acr samples obtained before gel filtration chromatography and compared with a gel-filtered sample. Results: The polynomial graphs constructed showed improved molecular coverage of the insulin B chain by the oligomer. The 2nd order coefficient is the one that changes with the oligomeric ratio of Acr and improves chaperone activity. Polynomial analysis suggested that it could be a useful parameter to predict chaperone activity for potential in vitro batches of M. tuberculosis Acr based on the dynamic nature of the association and disassociation of oligomers. Conclusions: The results showed that coverage of insulin B chain improved with higher ratio of 9-mer as compared to lower ratios. This was shown by both simulation plots and actual assay data. The polynomial graphs showed increase in the 2nd order coefficient, thus suggesting the important role of oligomerisation in improved molecular coverage of insulin B chain.
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spelling doaj.art-57ed67dcf0cf4bdd862b0a3dc9f896a22022-12-22T02:34:14ZengF1000 Research LtdF1000Research2046-14022018-11-01710.12688/f1000research.16328.117837Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs [version 1; peer review: 2 approved]Gautam Krishnan0Utpal Roy1Department of Biological Sciences, Birla Institute of Technology and Science, Zuari Nagar, Goa, 403726, IndiaDepartment of Biological Sciences, Birla Institute of Technology and Science, Zuari Nagar, Goa, 403726, IndiaBackground: Mycobacterial α-crystallin (Acr) is a chaperone that prevents misfolding of proteins when Mycobacterium tuberculosis is found in a latent form in the host tissue. Methods: Using insulin as a model substrate and utilizing polynomial graphs, we attempted to predict molecular-level interactions that are a function of the oligomeric state of the recombinant protein. The chaperone activity of the recombinant oligomeric Acr was measured at 60°C with Acr samples obtained before gel filtration chromatography and compared with a gel-filtered sample. Results: The polynomial graphs constructed showed improved molecular coverage of the insulin B chain by the oligomer. The 2nd order coefficient is the one that changes with the oligomeric ratio of Acr and improves chaperone activity. Polynomial analysis suggested that it could be a useful parameter to predict chaperone activity for potential in vitro batches of M. tuberculosis Acr based on the dynamic nature of the association and disassociation of oligomers. Conclusions: The results showed that coverage of insulin B chain improved with higher ratio of 9-mer as compared to lower ratios. This was shown by both simulation plots and actual assay data. The polynomial graphs showed increase in the 2nd order coefficient, thus suggesting the important role of oligomerisation in improved molecular coverage of insulin B chain.https://f1000research.com/articles/7-1801/v1
spellingShingle Gautam Krishnan
Utpal Roy
Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs [version 1; peer review: 2 approved]
F1000Research
title Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs [version 1; peer review: 2 approved]
title_full Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs [version 1; peer review: 2 approved]
title_fullStr Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs [version 1; peer review: 2 approved]
title_full_unstemmed Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs [version 1; peer review: 2 approved]
title_short Prediction of recombinant Mycobacterium tuberculosis α-crystallin oligomer chaperone activity using polynomial graphs [version 1; peer review: 2 approved]
title_sort prediction of recombinant mycobacterium tuberculosis α crystallin oligomer chaperone activity using polynomial graphs version 1 peer review 2 approved
url https://f1000research.com/articles/7-1801/v1
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AT utpalroy predictionofrecombinantmycobacteriumtuberculosisacrystallinoligomerchaperoneactivityusingpolynomialgraphsversion1peerreview2approved