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This article is part of the supplement: Eleventh International Conference on Bioinformatics (InCoB2012): Computational Biology

Open Access Proceedings

In silico engineering of aggregation-prone recombinant proteins for substrate recognition by the chaperonin GroEL

Vipul Kumar1, Ankita Punetha23, Durai Sundar2* and Tapan K Chaudhuri1*

Author Affiliations

1 School of Biological Sciences, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India

2 Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India

3 Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, India

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BMC Genomics 2012, 13(Suppl 7):S22  doi:10.1186/1471-2164-13-S7-S22

Published: 13 December 2012

Abstract

Background

Molecular chaperones appear to have been evolved to facilitate protein folding in the cell through entrapment of folding intermediates on the interior of a large cavity formed between GroEL and its co-chaperonin GroES. They bind newly synthesized or non-native polypeptides through hydrophobic interactions and prevent their aggregation. Some proteins do not interact with GroEL, hence even though they are aggregation prone, cannot be assisted by GroEL for their folding.

Results

In this study, we have attempted to engineer these non-substrate proteins to convert them as the substrate for GroEL, without compromising on their function. We have used a computational biology approach to generate mutants of the selected proteins by selectively mutating residues in the hydrophobic patch, similar to GroES mobile loop region that are responsible for interaction with GroEL, and compared with the wild counterparts for calculation of their instability and aggregation propensities. The energies of the newly designed mutants were computed through molecular dynamics simulations. We observed increased aggregation propensity of some of the mutants formed after replacing charged amino acid residues with hydrophobic ones in the well defined hydrophobic patch, raising the possibility of their binding ability to GroEL.

Conclusions

The newly generated mutants may provide potential substrates for Chaperonin GroEL, which can be experimentally generated and tested for their tendency of aggregation, interactions with GroEL and the possibility of chaperone-assisted folding to produce functional proteins.