Analysis of anisotropic side-chain packing in proteins and application to high-resolution structure prediction

Kira M.S. Misura, Alexandre V. Morozov, David Baker

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


π-π, cation-π, and hydrophobic packing interactions contribute specificity to protein folding and stability to the native state. As a step towards developing improved models of these interactions in proteins, we compare the side-chain packing arrangements in native proteins to those found in compact decoys produced by the Rosetta de novo structure prediction method. We find enrichments in the native distributions for T-shaped and parallel offset arrangements of aromatic residue pairs, in parallel stacked arrangements of cation-aromatic pairs, in parallel stacked pairs involving proline residues, and in parallel offset arrangements for aliphatic residue pairs. We then investigate the extent to which the distinctive features of native packing can be explained using Lennard-Jones and electrostatics models. Finally, we derive orientation-dependent π-π, cation-π and hydrophobic interaction potentials based on the differences between the native and compact decoy distributions and investigate their efficacy for high-resolution protein structure prediction. Surprisingly, the orientation-dependent potential derived from the packing arrangements of aliphatic side-chain pairs distinguishes the native structure from compact decoys better than the orientation-dependent potentials describing π-π and cation-π interactions.

Original languageEnglish (US)
Pages (from-to)651-664
Number of pages14
JournalJournal of molecular biology
Issue number2
StatePublished - Sep 10 2004

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology


  • Rosetta
  • hydrophobic core
  • potential energy function
  • protein structure prediction
  • side-chain packing

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