Carboxylic acids in crystallization of macromolecules: learning from successful crystallization experiments

• Published in: Journal of structural and functional genomics 2014-03, Vol.15 (1), p.13-24
• Main Authors: Offermann, Lesa R., He, John Z., Mank, Nicholas J., Booth, William T., Chruszcz, Maksymilian
• Format: Article
• Language: English
• Subjects: Acetates - chemistry; Acids; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Carboxylic Acids - chemistry; Citrates - chemistry; Crystallization; Crystallography, X-Ray; Crystals; Data mining; Datasets; Experiments; Forestry Management; Formates - chemistry; Human Genetics; Hydrogen-Ion Concentration; Life Sciences; Ligands; Macromolecular Substances - chemistry; Microbial Genetics and Genomics; Plant Genetics and Genomics; Polyethylene glycol; Proteins; Proteins - chemistry; Salts - chemistry; Trends
• ISSN: 1345-711X; 1570-0267
• DOI: 10.1007/s10969-014-9171-4

The production of macromolecular crystals suitable for structural analysis is one of the most important and limiting steps in the structure determination process. Often, preliminary crystallization trials are performed using hundreds of empirically selected conditions. Carboxylic acids and/or their salts are one of the most popular components of these empirically derived crystallization conditions. Our findings indicate that almost 40 % of entries deposited to the Protein Data Bank (PDB) reporting crystallization conditions contain at least one carboxylic acid. In order to analyze the role of carboxylic acids in macromolecular crystallization, a large-scale analysis of the successful crystallization experiments reported to the PDB was performed. The PDB is currently the largest source of crystallization data, however it is not easily searchable. These complications are due to a combination of a free text format, which is used to capture information on the crystallization experiments, and the inconsistent naming of chemicals used in crystallization experiments. Despite these difficulties, our approach allows for the extraction of over 47,000 crystallization conditions from the PDB. Initially, the selected conditions were investigated to determine which carboxylic acids or their salts are most often present in crystallization solutions. From this group, selected sets of crystallization conditions were analyzed in detail, assessing parameters such as concentration, pH, and precipitant used. Our findings will lead to the design of new crystallization screens focused around carboxylic acids.