title: Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data.
abstract: Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of entire predicted proteomes demonstrate substantial differences in the amino acid-sequence properties of human versus eubacterial proteins, which likely reflect differences in biophysical properties, including crystallization propensity. Our thermodynamic measurements do not generally support previous claims regarding correlations between sequence properties and protein stability.
authors.affiliation: Northeast Structural Genomics Consortium, Columbia University, New York, New York 10027, USA.
authors.forename: W Nicholson
authors.initials: WN
authors.lastname: Price
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Handelman
authors.forename: Helen
authors.initials: H
authors.lastname: Neely
authors.forename: Philip
authors.initials: P
authors.lastname: Manor
authors.forename: Richard
authors.initials: R
authors.lastname: Karlin
authors.forename: Rajesh
authors.initials: R
authors.lastname: Nair
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Michael
authors.initials: M
authors.lastname: Baran
authors.forename: John
authors.initials: J
authors.lastname: Everett
authors.forename: Saichiu N
authors.initials: SN
authors.lastname: Tong
authors.forename: Farhad
authors.initials: F
authors.lastname: Forouhar
authors.forename: Swarup S
authors.initials: SS
authors.lastname: Swaminathan
authors.forename: Thomas
authors.initials: T
authors.lastname: Acton
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Luft
authors.forename: Angela
authors.initials: A
authors.lastname: Lauricella
authors.forename: George T
authors.initials: GT
authors.lastname: DeTitta
authors.forename: Burkhard
authors.initials: B
authors.lastname: Rost
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
authors.forename: John F
authors.initials: JF
authors.lastname: Hunt
mesh_terms: D000465:Algorithms; D000818:Animals; D001703:Biophysics / Q000379:methods; D019295:Computational Biology / Q000379:methods; D003460:Crystallization; D019277:Entropy; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D015233:Models, Statistical; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: D000939:Epitopes; D011506:Proteins