Understanding the relationship between protein structure
and experimental
data is crucial for utilizing experiments to solve biochemical problems
and optimizing the use of sparse experimental data for structural
interpretation. Tandem mass spectrometry (MS/MS) can be used with
a variety of methods to collect structural data for proteins. One
example is surface-induced dissociation (SID), which is used to break
apart protein complexes (via a surface collision) into intact subcomplexes
and can be performed at multiple laboratory frame SID collision energies.
These energy-resolved MS/MS experiments have shown that the profile
of the breakages depends on the acceleration energy of the collision.
It is possible to extract an appearance energy (AE) from energy-resolved
mass spectrometry (ERMS) data, which shows the relative intensity
of each type of subcomplex as a function of SID acceleration energy.
We previously determined that these AE values for specific interfaces
correlated with structural features related to interface strength.
In this study, we further examined the structural relationships by
developing a method to predict the full ERMS plot from the structure,
rather than extracting a single value. First, we noted that for proteins
with multiple interface types, we could reproduce the correct shapes
of breakdown curves, further confirming previous structural hypotheses.
Next, we demonstrated that interface size and energy density (measured
using Rosetta) correlated with data derived from the ERMS plot (R
2 = 0.71). Furthermore, based on this trend,
we used native crystal structures to predict ERMS. The majority of
predictions resulted in good agreement, and the average root-mean-square
error was 0.20 for the 20 complexes in our data set. We also show
that if additional information on cleavage as a function of collision
energy could be obtained, the accuracy of predictions improved further.
Finally, we demonstrated that ERMS prediction results were better
for the native than for inaccurate models in 17/20 cases. An application
to run this simulation has been developed in Rosetta, which is freely
available for use.