PXS crystallization score and prediction server

Center

Northeast Structural Genomics Consortium

Technology

Crystallography

Summary

A paper describing data mining of the experimental results of the Northeast Structural Genomics Consortium to characterize the biophysical properties that control protein crystallization. The results of this analysis have lead to a crystallization probability score (PXS), and server (http://www.nesg.org/PXS ) which can be used to predict the crystallizability of a protein sequence.

Description

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 acidsequence 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.

Publication

1: Price WN 2nd, Chen Y, Handelman SK, Neely H, Manor P, Karlin R, Nair R, Liu J,Baran M, Everett J, Tong SN, Forouhar F, Swaminathan SS, Acton T, Xiao R, LuftJR, Lauricella A, DeTitta GT, Rost B, Montelione GT, Hunt JF. Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data. Nat Biotechnol. 2009 Jan;27(1):51-7. PubMed PMID: 19079241. Pubmed:19079241 | Search SGKB Publications portal