Quaternary structure prediction is of great importance, as most proteins exist as complexes in vivo. In this study, we use experimental data from surface-induced dissociation (SID) coupled with mass spectrometry (MS) to improve protein-protein docking in Rosetta. SID is a technique that can provide information about complex stoichiometry and the relative energy barrier of breaking the mostly non-covalent interactions at protein-protein interfaces. In SID, protein complexes are ionized and accelerated towards a rigid surface at varying energies. Upon contact with the surface, the subunits dissociate differently depending on acceleration energy. The resulting protein fragments are subsequently analyzed with MS, which allows for measurement of the appearance energy (AE) of the broken interfaces, as well as complex stoichiometry. In a first step, we used multiple structure-based interface values such as interface area to correlate with SID AE measurements. We have shown that there is a strong correlation between these structural features and experimental SID appearance energy. Computationally, we use this information to implement a general, structure-based method for predicting interface appearance energy. This allows for discrimination of different quaternary structural models based on SID measurements in the form of a novel SID based scoring function, which is used in combination with Rosetta’s scoring function. This scoring function has been successful in rescoring experiments, improving Rosetta’s ability to select native-like poses.

Translating data from surface-induced dissociation mass spectrometry (SID-MS) into high-resolution structures of protein complexes

2019 Spring National Meeting

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