Prediction of membrane separation efficiency for hydrophobic and hydrophilic proteins A coarse-grained Brownian dynamics simulation study

• Published in: Journal of molecular modeling Vol. 25; no. 5; p. 132
• Main Authors: Zhang, Yushan, Zhang, Yong, McCready, Mark J., Maginn, Edward J.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-05-2019
• Subjects: Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Molecular Medicine; Original Paper; Theoretical and Computational Chemistry; Protein separations; Brownian dynamics simulation; Hydrophobicity; Separation efficiency
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-019-3985-8

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 (A
β
-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 A
β
-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.
Graphical Abstract
Simulation setup and snapshots of protein in various pore sizes