Computational study of elements of stability of a four-helix bundle protein biosurfactant

Schaller, Andrea, Connors, Natalie K., Dwyer, Mirjana Dimitrijev, Oelmeier, Stefan A., Hubbuch, Jurgen and Middelberg, Anton P. J. (2015) Computational study of elements of stability of a four-helix bundle protein biosurfactant. Journal of Computer-Aided Molecular Design, 29 1: 47-58. doi:10.1007/s10822-014-9803-6

Author Schaller, Andrea
Connors, Natalie K.
Dwyer, Mirjana Dimitrijev
Oelmeier, Stefan A.
Hubbuch, Jurgen
Middelberg, Anton P. J.
Title Computational study of elements of stability of a four-helix bundle protein biosurfactant
Journal name Journal of Computer-Aided Molecular Design   Check publisher's open access policy
ISSN 1573-4951
Publication date 2015-01
Year available 2014
Sub-type Article (original research)
DOI 10.1007/s10822-014-9803-6
Open Access Status
Volume 29
Issue 1
Start page 47
End page 58
Total pages 12
Place of publication Dordrecht, Netherlands
Publisher Springer Netherlands
Collection year 2015
Language eng
Abstract Biosurfactants are surface-active molecules produced principally by microorganisms. They are a sustainable alternative to chemically-synthesized surfactants, having the advantages of being non-toxic, highly functional, eco-friendly and biodegradable. However they are currently only used in a few industrial products due to costs associated with production and purification, which exceed those for commodity chemical surfactants. DAMP4, a member of a four-helix bundle biosurfactant protein family, can be produced in soluble form and at high yield in Escherichia coli, and can be recovered using a facile thermal phase-separation approach. As such, it encompasses an interesting synergy of biomolecular and chemical engineering with prospects for low-cost production even for industrial sectors. DAMP4 is highly functional, and due to its extraordinary thermal stability it can be purified in a simple two-step process, in which the combination of high temperature and salt leads to denaturation of all contaminants, whereas DAMP4 stays stable in solution and can be recovered by filtration. This study aimed to characterize and understand the fundamental drivers of DAMP4 stability to guide further process and surfactant design studies. The complementary use of experiments and molecular dynamics simulation revealed a broad pH and temperature tolerance for DAMP4, with a melting point of 122.4 °C, suggesting the hydrophobic core as the major contributor to thermal stability. Simulation of systematically created in silico variants of DAMP4 showed an influence of number and location of hydrophilic mutations in the hydrophobic core on stability, demonstrating a tolerance of up to three mutations before a strong loss in stability occurred. The results suggest a consideration of a balance of stability, functionality and kinetics for new designs according to their application, aiming for maximal functionality but at adequate stability to allow for cost-efficient production using thermal phase separation approaches.
Keyword MD simulation
Four-helix bundle
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 17 Oct 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 1 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 13 Jan 2015, 00:34:47 EST by System User on behalf of Aust Institute for Bioengineering & Nanotechnology