Mining biochemical information: lessons taught by the ribosome

Area of Science:

• Structural Biology
• Biochemistry
• Biophysics

Background:

• The advent of high-resolution ribosome crystal structures provides a unique opportunity to assess the validity of prior biochemical and biophysical data.
• Hundreds of studies have generated experimental proximity measurements for ribosomal components.

Purpose of the Study:

• To retrospectively evaluate the information content of experimental proximity measurements against known ribosomal crystal structures.
• To assess the correspondence between over 2,500 experimental proximity measurements and distances in ribosomal crystals.

Main Methods:

• Grouped and analyzed data from crosslinking, footprinting, and cleavage experiments.
• Compared experimental proximity measurements with distances derived from published ribosome crystal structures.
• Assessed the distribution and compatibility of experimental distances with structural models.

Main Results:

• Experimental distances generally fell within expected ranges based on agent length and crystal conformations.
• Observed heavier-than-expected tails in the distance distributions, indicating a higher fraction of incompatible measurements.
• Identified experimental methods and component properties (reactivity, flexibility, interactions) as factors influencing data accuracy.

Conclusions:

• Experimental proximity measurements offer valuable, albeit broadly distributed, distance information for structural modeling.
• A careful analysis of experimental data, considering all influencing parameters, is crucial for accurate structural modeling.
• Improved annotation of experimental data is needed to enhance automated modeling approaches and interpret significance.