Membrane Protein Engineering with Rosetta

Rebecca F Alford; Jeffrey J Gray

doi:10.1007/978-1-0716-1468-6_3

Membrane Protein Engineering with Rosetta

Methods Mol Biol. 2021:2315:43-57. doi: 10.1007/978-1-0716-1468-6_3.

Authors

Rebecca F Alford¹, Jeffrey J Gray^{2

3}

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
² Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA. jgray@jhu.edu.
³ Program in Molecular Biophysics, Johns Hopkins University, Baltimore, MD, USA. jgray@jhu.edu.

Abstract

Protein engineering can yield new molecular tools for nanotechnology and therapeutic applications through modulating physiochemical and biological properties. Engineering membrane proteins is especially attractive because they perform key cellular processes including transport, nutrient uptake, removal of toxins, respiration, motility, and signaling. In this chapter, we describe two protocols for membrane protein engineering with the Rosetta software: (1) ΔΔG calculations for single point mutations and (2) sequence optimization in different membrane lipid compositions. These modular protocols are easily adaptable for more complex problems and serve as a foundation for efficient membrane protein engineering calculations.

Keywords: Implicit membrane; Lipid composition; Monte Carlo; Protein design; Rosetta.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Biological Transport / physiology
Membrane Lipids / chemistry
Membrane Lipids / metabolism
Membrane Proteins / chemistry*
Membrane Proteins / metabolism*
Membranes / chemistry*
Membranes / metabolism*
Models, Molecular
Protein Engineering / methods*
Software

Substances

Membrane Lipids
Membrane Proteins

Grants and funding

R01 GM078221/GM/NIGMS NIH HHS/United States