This notebook contains material from PyRosetta; content is available on Github.

Modeling Membrane Proteins


Membrane protiens constitute 30% of all proteins and are targets for 60% of pharmeceuticals on the market. These biomolecules are unique because their structure and function is coupled with the lipid bilayer: a self-assembling nanostructure made from hundreds of lipid types such as phospholipids and cholesterol. The goals of this workshop are to (1) learn common tasks for membrane protein modeling in PyRosetta and (2) give examples of the types of problems one can solve with this framework.

Learning Objectives

  1. Use membrane tools to orient a protein in the lipid bilayer
  2. Identify and visualize membrane protein pores and cavities
  3. Apply membrane tools to obtain membrane data for modeling
  4. Interpret model quality using terms from franklin2019, the membrane energy function
  5. Illustrative example of predicting the ∆∆G of mutation within the bilayer
  6. Illustrative example of membrane protein-protein docking

Suggested Readings

  1. Alford RF, Leman JK et al., “An Integrated Framework Advancing Membrane Protein Modeling and Design,” PLOS Computational Biology. 2015;11(9).
  2. Alford RF, Fleming PJ, Fleming KG, Gray JJ (2020) “Protein structure prediction and design in a biologically-realistic implicit membrane” BioRxiv
  3. Koehler Leman J, Muller BK, Gray JJ (2017) “Expanding the toolkit for membrane protein modeling in Rosetta” Bioinformatics 33(5):754-756.
  4. Koehler Leman J & Gray JJ (2015) “Computational modeling of membrane proteins” Proteins Structure, Function, and Bioinformatics 83(1):1-24.

Chapter Contributors

  • Rebecca Alford (Johns Hopkins University)
  • Kathy Le (Johns Hopkins University)
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