The structural genomics experimental pipeline: insights from global target lists

Area of Science:

• Structural biology
• Genomics
• Biophysics

Background:

• Structural genomics (SG) aims for high-throughput, genome-wide protein structure determination.
• Assessing the efficiency and potential of current SG initiatives is crucial.

Purpose of the Study:

• To analyze publicly released SG target data over 16 months.
• To evaluate the potential and efficiency of structural genomics initiatives.

Main Methods:

• Statistical analysis, commonly used in epidemiology, was applied to track targets through the SG pipeline.
• Analysis of cloning, expression, purification, crystallization, diffraction, and HSQC data.

Main Results:

• No single bottleneck identified in the SG pipeline; each step has ~45% progression probability.
• Crystal structures obtained from ~80% of targets with diffraction data; NMR structures from ~20% with HSQC spectra.
• 61% of SG targets share significant sequence identity (>30%) with others; SG structures are deposited twice as fast post-X-ray data collection.

Conclusions:

• Structural genomics pipelines demonstrate consistent, albeit not bottleneck-free, progression.
• SG structures are comparable in quality to traditionally determined structures and are deposited more rapidly.