Protein dynamics governed by interfaces of high polarity and low packing density

PLoS One. 2012;7(10):e48212. doi: 10.1371/journal.pone.0048212. Epub 2012 Oct 26.


The folding pathway, three-dimensional structure and intrinsic dynamics of proteins are governed by their amino acid sequences. Internal protein surfaces with physicochemical properties appropriate to modulate conformational fluctuations could play important roles in folding and dynamics. We show here that proteins contain buried interfaces of high polarity and low packing density, coined as LIPs: Light Interfaces of high Polarity, whose physicochemical properties make them unstable. The structures of well-characterized equilibrium and kinetic folding intermediates indicate that the LIPs of the corresponding native proteins fold late and are involved in local unfolding events. Importantly, LIPs can be identified using very fast and uncomplicated computational analysis of protein three-dimensional structures, which provides an easy way to delineate the protein segments involved in dynamics. Since LIPs can be retained while the sequences of the interacting segments diverge significantly, proteins could in principle evolve new functional features reusing pre-existing encoded dynamics. Large-scale identification of LIPS may contribute to understanding evolutionary constraints of proteins and the way protein intrinsic dynamics are encoded.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins
  • Cytochromes c / chemistry
  • Indole-3-Glycerol-Phosphate Synthase / chemistry
  • Kinetics
  • Lactalbumin / chemistry
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Ribonucleases / chemistry


  • Bacterial Proteins
  • Proteins
  • Cytochromes c
  • Lactalbumin
  • Ribonucleases
  • Bacillus amyloliquefaciens ribonuclease
  • Indole-3-Glycerol-Phosphate Synthase

Grants and funding

VEA was supported by Banco Santander Central Hispano, Fundación Carolina and Universidad de Zaragoza and is now a recipient of a JAE-CSIC doctoral fellowship. JS would like to acknowledge financial support from grants BFU2010-16297 [Ministerio de Ciencia e Innovación (MICINN), Spain] and Grupo Protein Targets B89 [DGA, Spain]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.