Computational design of a water-soluble analog of phospholamban

Protein Sci. 2003 Feb;12(2):337-48. doi: 10.1110/ps.0226603.


Membrane proteins and water-soluble proteins share a similar core. This similarity suggests that it should be possible to water-solubilize membrane proteins by mutating only their lipid-exposed residues. We have developed computational tools to design water-soluble variants of helical membrane proteins, using the pentameric phospholamban (PLB) as our test case. To water-solublize PLB, the membrane-exposed positions were changed to polar or charged amino acids, while the putative core was left unaltered. We generated water-soluble phospholamban (WSPLB), and compared its properties to its predecessor PLB. In aqueous solution, WSPLB mimics all of the reported properties of PLB including oligomerization state, helical structure, and stabilization upon phosphorylation. We also characterized the truncated mutant WSPLB (21-52) comprising only the former transmembrane segment of PLB. This peptide shows a decreased specificity for forming a pentameric oligomerization state.

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Calcium-Binding Proteins / chemistry*
  • Circular Dichroism
  • Computer-Aided Design*
  • Drug Design
  • Membrane Proteins / chemistry*
  • Molecular Sequence Data
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Phosphorylation
  • Protein Denaturation
  • Protein Engineering*
  • Protein Structure, Quaternary
  • Solubility
  • Thermodynamics
  • Water / chemistry*


  • Calcium-Binding Proteins
  • Membrane Proteins
  • Peptide Fragments
  • phospholamban
  • Water