Net charge per residue modulates conformational ensembles of intrinsically disordered proteins

Albert H. Mao, Scott L. Crick, Andreas Vitalis, Caitlin L. Chicoine, Rohit V. Pappu

Research output: Contribution to journalArticlepeer-review

386 Scopus citations


Intrinsically disordered proteins (IDPs) adopt heterogeneous ensembles of conformations under physiological conditions. Understanding the relationship between amino acid sequence and conformational ensembles of IDPs can help clarify the role of disorder in physiological function. Recent studies revealed that polar IDPs favor collapsed ensembles in water despite the absence of hydrophobic groups - a result that holds for polypeptide backbones as well. By studying highly charged polypeptides, a different archetype of IDPs, we assess how charge content modulates the intrinsic preference of polypeptide backbones for collapsed structures. We characterized conformational ensembles for a set of protamines in aqueous milieus using molecular simulations and fluorescence measurements. Protamines are arginine-rich IDPs involved in the condensation of chromatin during spermatogenesis. Simulations based on the ABSINTH implicit solvation model predict the existence of a globule-to-coil transition, with net charge per residue serving as the discriminating order parameter. The transition is supported by quantitative agreement between simulation and experiment. Local conformational preferences partially explain the observed trends of polymeric properties. Our results lead to the proposal of a schematic protein phase diagram that should enable prediction of polymeric attributes for IDP conformational ensembles using easily calculated physicochemical properties of amino acid sequences. Although sequence composition allows the prediction of polymeric properties, interresidue contact preferences of protamines with similar polymeric attributes suggest that certain details of conformational ensembles depend on the sequence. This provides a plausible mechanism for specificity in the functions of IDPs.

Original languageEnglish
Pages (from-to)8183-8188
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number18
StatePublished - May 4 2010


  • Monte Carlo
  • Polyampholyte
  • Polyelectrolyte


Dive into the research topics of 'Net charge per residue modulates conformational ensembles of intrinsically disordered proteins'. Together they form a unique fingerprint.

Cite this