(773h) Full-Atom Molecular Simulations of Lysozyme Confined in Realistic Silica Mesopores – Insights in Conformation and Accessibility of Active Sites

Confinement of biomolecules in ordered mesoporous materials is receiving growing attention, because of potential applications in drug delivery systems, as well as in bio-separations and bio-catalysis. Experiments with mesoporous silica SBA-15 demonstrated that this material can be used to stabilize enzymes thanks to spatial and electrostatic confinement effects, similar to what is seen in the GroEL/GroES chaperonin complex [1]. In particular, experimental results of hen egg white lysozyme immobilized on SBA-15 show that the pore surface properties (curvature, electric charge and hydrophobicity), as well as the solute properties (pH and ionic strength) play a significant role in the stability of the confined enzyme, as well as its associated catalytic activity [2].

Because of this, it is of interest to systematically investigate the interactions between proteins and the pore surface of mesoporous materials, to explain how charge and surface curvature, related to pore size, dictate the protein’s orientation and affect the accessibility of its active site. A recent series of theoretical studies has shown that protein adsorption on a surface, modelled to represent silica, is mainly driven by electrostatic forces with positively charged residues helping to anchor the enzyme to the silica wall [3-7].

We have carried out new studies to understand the complex process of lysozyme adsorption on a realistic, curved silica mesopore surface. In these studies, we investigate the behavior of lysozyme in contact with a realistic representation of a pore of SBA-15, as used in complementary experimental work [1,2]. This representation includes pore roughness. We perform restrained all-atom molecular dynamics (MD) simulations, and we discuss our insights concerning how electrostatic and steric effects of the silica boundary induce conformational changes, and affect the accessibility of the active site of a confined lysozyme molecule.

REFERENCES

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[2] M. Lynch, J. Liu, M. Nigra, and M-O Coppens; Langmuir 32, 9604- 9610, 2016

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[4] K. Kubiak-Ossowska, P.A. Mulheran, Langmuir 26, 7690-7694, 2010

[5] K. Kubiak-Ossowska, P.A. Mulheran, Langmuir 26, 15954-15965, 2010

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