Identifying and Overcoming Crystal Pathologies: Disorder and Twinning

Abstract

Macromolecular crystals are prone to a number of pathologies that result from aberrant molecular packing. Two common pathologies encountered in macromolecular crystals are rigid-body disorder and twinning. When a crystal displays one of these pathologies, its diffraction pattern is altered in a way that generally complicates structure determination. The severity of the underlying abnormalities varies from case to case, and sometimes the resulting alterations to the diffraction pattern are immediately obvious, while at other times they may go entirely unnoticed. Structure determination from a crystal that suffers from disorder or twinning may or may not be possible, depending on the specific nature of the pathology, and on how the data are handled. This chapter provides an introduction to these pathologies, with an emphasis on providing guidelines for identifying and overcoming them when they pose a threat to successful structure determination.

X-ray diffraction and in vivo studies reveal the quinary structure of Trypanosoma cruzi nucleoside diphosphate kinase 1: a novel helical oligomer structure

“…Data processing and statistical analysis of the data were performed with TRUNCATE (from CCP4), which permits the use of the H-test (Yeates, 1988) and L-test (Padilla & Yeates, 2003). The L-test is considered to be the most robust statistical test for twinning in macromolecular crystallography (Thompson, 2017;Campeotto et al, 2018). The L-test prediction is also performed internally in REFMAC5 (Murshudov et al, 2011) to estimate the twinning fraction during refinement.…”

Computational design of a modular protein sense/response system

“…Specifically, we identified an FPP molecule occupying one of the computationally-designed binding sites, as well as two maltose disaccharides (one bound to each copy of MBP). The presence of merohedral twinning can present challenges for map interpretation because the structure factor detwinning process can exacerbate the effects of model phase bias (29). Consequently, we took extra care with the placement of the FPP ligand into electron density features around the designed binding site.…”

Color Control in Bis-ethylenedioxythiophene Phenylene Anodically Coloring Electrochromes

“…This difference may be attributed to disorder found in the X-ray structure that generates two overlapping alternative conformations that resulted from a crystal growth abnormality. 43,44 Outside of these two discrepancies, these comparisons show that DFT calculations provide reliable insight into the electrostatic interactions and structural conformation of the molecules, which allows elucidation of structure−property relationships that will be carried out throughout this work.…”