PoreDesigner for tuning solute selectivity in a robust and highly permeable outer membrane pore

Ratul Chowdhury,Jeevan Prabhakar,Manish Shankla,Aleksei Aksimentiev,Costas D Maranas,Matthew Grisewood,Carol Baker,Manish Kumar,John H Golbeck,Karl Decker,Tingwei Ren

doi:10.1038/s41467-018-06097-1

Ratul Chowdhury, Jeevan Prabhakar + Show 9 more

Open Access

https://doi.org/10.1038/s41467-018-06097-1

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Abstract

Monodispersed angstrom-size pores embedded in a suitable matrix are promising for highly selective membrane-based separations. They can provide substantial energy savings in water treatment and small molecule bioseparations. Such pores present as membrane proteins (chiefly aquaporin-based) are commonplace in biological membranes but difficult to implement in synthetic industrial membranes and have modest selectivity without tunable selectivity. Here we present PoreDesigner, a design workflow to redesign the robust beta-barrel Outer Membrane Protein F as a scaffold to access three specific pore designs that exclude solutes larger than sucrose (>360 Da), glucose (>180 Da), and salt (>58 Da) respectively. PoreDesigner also enables us to design any specified pore size (spanning 3–10 Å), engineer its pore profile, and chemistry. These redesigned pores may be ideal for conducting sub-nm aqueous separations with permeabilities exceeding those of classical biological water channels, aquaporins, by more than an order of magnitude at over 10 billion water molecules per channel per second.

Highlights

Monodispersed angstrom-size pores embedded in a suitable matrix are promising for highly selective membrane-based separations
We worked with the trimeric Escherichia coli protein outer membrane porin type F (OmpF, wild-type (WT) pore size of ~ 11 Å) to attain desired pore sizes that could enable precise molecular separations
Aquaporins have the ideal internal pore geometry for selective and highly permeable water channels but the pore wall interacts strongly with the permeating water wire[47], indicating the possibility of enhancing permeability at similar size ranges without sacrificing selectivity

Summary

Introduction

Monodispersed angstrom-size pores embedded in a suitable matrix are promising for highly selective membrane-based separations They can provide substantial energy savings in water treatment and small molecule bioseparations. PoreDesigner enables us to design any specified pore size (spanning 3–10 Å), engineer its pore profile, and chemistry These redesigned pores may be ideal for conducting sub-nm aqueous separations with permeabilities exceeding those of classical biological water channels, aquaporins, by more than an order of magnitude at over 10 billion water molecules per channel per second. AQP-based membranes do not allow for selective removal of larger solutes in the sub-nm range To this end, we put forth a predictive platform to computationally redesign the pore-constricting residues of a highly stable outer membrane protein[31] of β-barrel family of channels present in bacteria[32]. It can be assembled into stable two-dimensional crystals formed within block-copolymer membrane matrices[41] which may be ideal for preparation of larger scale separation membranes[19]

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