Geometric analysis of cross-linkability for protein fold discrimination.

Protein structure provides insight into the evolutionary origins, functions, and mechanisms of proteins. We are pursuing a minimalist approach to protein fold identification that characterizes possible folds in terms of consistency of their geometric features with restraints derived from relatively cheap, high-throughput experiments. One such experiment is residue-specific cross-linking analyzed by mass spectrometry. This paper presents a suite of novel lower- and upper-bounding algorithms for analyzing the distance between surface cross-link sites and thereby validating predicted models against experimental cross-linking results. Through analysis and computational experiments, using simulated and published experimental data, we demonstrate that our algorithms enable effective model discrimination.