Faculty Collaboration Database

You are lost without a map: Navigating the sea of protein structures. Biochim Biophys Acta 2015 Apr;1854(4):258-68

Date

01/03/2015

Pubmed ID

25554228

Pubmed Central ID

PMC5051661

DOI

10.1016/j.bbapap.2014.12.021

Scopus ID

2-s2.0-84921044740 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

X-ray crystal structures propel biochemistry research like no other experimental method, since they answer many questions directly and inspire new hypotheses. Unfortunately, many users of crystallographic models mistake them for actual experimental data. Crystallographic models are interpretations, several steps removed from the experimental measurements, making it difficult for nonspecialists to assess the quality of the underlying data. Crystallographers mainly rely on "global" measures of data and model quality to build models. Robust validation procedures based on global measures now largely ensure that structures in the Protein Data Bank (PDB) are largely correct. However, global measures do not allow users of crystallographic models to judge the reliability of "local" features in a region of interest. Refinement of a model to fit into an electron density map requires interpretation of the data to produce a single "best" overall model. This process requires inclusion of most probable conformations in areas of poor density. Users who misunderstand this can be misled, especially in regions of the structure that are mobile, including active sites, surface residues, and especially ligands. This article aims to equip users of macromolecular models with tools to critically assess local model quality. Structure users should always check the agreement of the electron density map and the derived model in all areas of interest, even if the global statistics are good. We provide illustrated examples of interpreted electron density as a guide for those unaccustomed to viewing electron density.

Author List

Lamb AL, Kappock TJ, Silvaggi NR

Author

Nicholas R. Silvaggi PhD Assistant Professor in the Chemistry and Biochemistry department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Crystallography, X-Ray
Databases, Protein
Electrons
Humans
Ligands
Macromolecular Substances
Models, Molecular
Protein Conformation
Protein Interaction Maps
Proteins