title: Statistical analysis of crystallization database links protein physico-chemical features with crystallization mechanisms.
abstract: X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds through knowledge-informed empiricism. Better physico-chemical understanding remains elusive because of the large number of variables involved, hence little guidance is available to systematically identify solution conditions that promote crystallization. To help determine relationships between macromolecular properties and their crystallization propensity, we have trained statistical models on samples for 182 proteins supplied by the Northeast Structural Genomics consortium. Gaussian processes, which capture trends beyond the reach of linear statistical models, distinguish between two main physico-chemical mechanisms driving crystallization. One is characterized by low levels of side chain entropy and has been extensively reported in the literature. The other identifies specific electrostatic interactions not previously described in the crystallization context. Because evidence for two distinct mechanisms can be gleaned both from crystal contacts and from solution conditions leading to successful crystallization, the model offers future avenues for optimizing crystallization screens based on partial structural information. The availability of crystallization data coupled with structural outcomes analyzed through state-of-the-art statistical models may thus guide macromolecular crystallization toward a more rational basis.
authors.affiliation: Program in Computational Biology and Bioinformatics, Duke University, Durham, North Carolina, United States of America; Department of Chemistry, Duke University, Durham, North Carolina, United States of America.
authors.forename: Diana
authors.initials: D
authors.lastname: Fusco
authors.affiliation: Department of Chemistry, Duke University, Durham, North Carolina, United States of America; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Barnum
authors.affiliation: Center for Computational Research, State University of New York, Buffalo, New York, United States of America.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Bruno
authors.affiliation: Hauptman-Woodward Medical Research Institute, Buffalo, New York, United States of America.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Luft
authors.affiliation: Hauptman-Woodward Medical Research Institute, Buffalo, New York, United States of America; Department of Structural Biology, State University of New York, Buffalo, New York, United States of America.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Snell
authors.affiliation: Department of Statistical Science, Department of Computer Science and Department of Mathematics, Duke University, Durham, North Carolina, United States of America.
authors.forename: Sayan
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Chemistry, Duke University, Durham, North Carolina, United States of America; Department of Physics, Duke University, Durham, North Carolina, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Charbonneau
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods*; D030562:Databases, Protein; D008956:Models, Chemical; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins