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Prediction of membrane separation efficiency for hydrophobic and hydrophilic proteins

A coarse-grained Brownian dynamics simulation study

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Abstract

A coarse-grained Brownian dynamics model was used to simulate two proteins of similar sizes inside model membrane pores of varying size and hydrophobicity. The two proteins, which have radii of gyration of approximately 9.5 Å in their native states, are a 36-residue hydrophilic villin head piece (HP-36) and a 40-residue hydrophobic amyloid beta (Aβ-40). From calculations of the separation factor, it is found that the two proteins are best separated using a pore radius of 15 Å and that hydrophobic pores select Aβ-40 while the hydrophilic pores preferentially pass through HP-36. In addition, it is found that a simple model based on the net hydropathy of a protein is capable of estimating the separation factor trends of other protein pairs. Together, the coarse-grained Brownian dynamics model and the simple model are fast methodologies to guide experimental membrane design and to provide insights on protein structure variations.

Simulation setup and snapshots of protein in various pore sizes

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Acknowledgments

Funding for this project was provided by the National Science Foundation: Division of Chemical, Bioengineering, Environmental, and Transport Systems (1511862). Computational resources are provided by Notre Dame’s Center for Research Computing.

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  1. Department of Chemical and Biomolecular Engineering, University of Notre Dame, 182 Fitzpatrick Hall, Notre Dame, IN, 46556, USA

    Yushan Zhang, Yong Zhang, Mark J. McCready & Edward J. Maginn

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Zhang, Y., Zhang, Y., McCready, M.J. et al. Prediction of membrane separation efficiency for hydrophobic and hydrophilic proteins. J Mol Model 25, 132 (2019). https://doi.org/10.1007/s00894-019-3985-8

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