Statistical and conformational analysis of the electron density of protein side chains

Maxim V. Shapovalov, Roland L. Dunbrack

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Protein side chains make most of the specific contacts between proteins and other molecules, and their conformational properties have been studied for many years. These properties have been analyzed primarily in the form of rotamer libraries, which cluster the observed conformations into groups and provide frequencies and average dihedral angles for these groups. In recent years, these libraries have improved with higher resolution structures and using various criteria such as high thermal factors to eliminate side chains that may be misplaced within the crystallographic model coordinates. Many of these side chains have highly non-rotameric dihedral angles. The origin of side chains with high B-factors and/or with non-rotameric dihedral angles is of interest in the determination of protein structures and in assessing the prediction of side chain conformations. In this paper, using a statistical analysis of the electron density of a large set of proteins, it is shown that: (1) most non-rotameric side chains have low electron density compared to rotameric side chains; (2) up to 15% of χ1 non-rotameric side chains in PDB models can clearly be fit to density at a single rotameric conformation and in some cases multiple rotameric conformations; (3) a further 47% of non-rotameric side chains have highly dispersed electron density, indicating potentially inter-converting rotameric conformations; (4) the entropy of these side chains is close to that of side chains annotated as having more than one χ1 rotamer in the crystallographic model; (5) many rotameric side chains with high entropy clearly show multiple conformations that are not annotated in the crystallographic model. These results indicate that modeling of side chains alternating between retainers in the electron density is important and needs further improvement, both in structure determination and in structure prediction.

Original languageEnglish
Pages (from-to)279-303
Number of pages25
JournalProteins: Structure, Function and Bioinformatics
Volume66
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • Protein side chains
  • Rotamers
  • X-ray crystallography

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