Abstract
Proteomics methodology has expanded to include protein structural analysis, primarily through cross-linking mass spectrometry (XL-MS) and hydrogen–deuterium exchange mass spectrometry (HX-MS). However, while the structural proteomics community has effective tools for primary data analysis, there is a need for structure modeling pipelines that are accessible to the proteomics specialist. Integrative structural biology requires the aggregation of multiple distinct types of data to generate models that satisfy all inputs. Here, we describe IMProv, an app in the Mass Spec Studio that combines XL-MS data with other structural data, such as cryo-EM densities and crystallographic structures, for integrative structure modeling on high-performance computing platforms. The resource provides an easily deployed bundle that includes the open-source Integrative Modeling Platform program (IMP) and its dependencies. IMProv also provides functionality to adjust cross-link distance restraints according to the underlying dynamics of cross-linked sites, as characterized by HX-MS. A dynamics-driven conditioning of restraint values can improve structure modeling precision, as illustrated by an integrative structure of the five-membered Polycomb Repressive Complex 2. IMProv is extensible to additional types of data.
Highlights
Proteomics methodology has expanded to include protein structural analysis, primarily through cross-linking mass spectrometry (XL-MS) and hydrogen–deuterium exchange mass spectrometry (HX-MS)
While the structural proteomics community has effective tools for primary data analysis, there is a need for structure modeling pipelines that are accessible to the proteomics specialist
IMProv provides functionality to adjust cross-link distance restraints according to the underlying dynamics of cross-linked sites, as characterized by HX-MS
Summary
In Brief Proteomics has much to contribute to the structural analysis of cells, considering the new developments in computational structural prediction. The technique was used to stabilize complexes for the identification of new factors but with improved MS instrumentation and software, linked residues can be detected with accuracy This capability enables a deeper topological analysis of protein networks [1,2,3] and produces rich restraint sets for protein structure determination [4,5,6]. Flexible and dynamic protein systems sampled with the usual long-lived reaction chemistries are susceptible to kinetic trapping, a phenomenon where conformational transitions are cross-linked, resulting in restraint sets that are not representative of the equilibrium structure [33,34,35] Such heterogeneous structural data result in models with poor accuracy and precision and may preclude model convergence entirely [35]. The functionality of the app is described and tested by modeling the five-member Polycomb Repressive Complex 2 (PRC2) [49,50,51], a 300 kDa chromatin remodeling complex
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
