Federating Structural Models and Data: Outcomes from A Workshop on Archiving Integrative Structures

Abstract

Structures of biomolecular systems are increasingly computed by integrative modeling. In this approach, a structural model is constructed by combining information from multiple sources, including varied experimental methods and prior models. In 2019, a Workshop was held as a Biophysical Society Satellite Meeting to assess progress and discuss further requirements for archiving integrative structures. The primary goal of the Workshop was to build consensus for addressing the challenges involved in creating common data standards, building methods for federated data exchange, and developing mechanisms for validating integrative structures. The summary of the Workshop and the recommendations that emerged are presented here.

Integrative structure and function of the yeast exocyst complex

“…One approach to overcome the limitations of individual methods is integrative structure modeling 27–32,76–79 . Integrative modeling aims to simultaneously use all available information from any method, including from varied experiments (e.g., EM and chemical cross‐linking), physical theories (e.g., molecular mechanics force field), statistical analyses (e.g., statistical potentials), and prior models (e.g., atomic structures of complex subunits).…”

“…The architecture of the yeast exocyst complex was determined using the integrative structure modeling approach described previously 27–32,76–79 . All available structural information on the exocyst complex was used for computational analyses (Table S2, Figure 3, and Section 4).…”

Toward Increased Reliability, Transparency, and Accessibility in Cross-linking Mass Spectrometry

“…The chemistry of the cross-linking reagent should be well defined regarding reactive sites and spacer length to define appropriate boundaries for cross-link restraints. A stable link to the primary data is required, for example, in a proteomics repository, and the data need to be provided in standardized form (also a wwPDB Integrative/Hybrid Methods Task Force recommendation; Berman et al, 2019;Sali et al, 2015). The data should be findable and experimental details documented, i.e., some basic technical and biological metadata need to be associated with the data together with a link to a more detailed description, ideally a publication.…”

“…Encouraged by the Worldwide Protein Data Bank (wwPDB) Task Force for Integrative/Hybrid Methods (Berman et al, 2019;Sali et al, 2015) to provide experimentalists and modelers with a stable access point to cross-linking data, an initial open gathering on standards in the Cross-linking MS field took place at the 14 th Human Proteome Organization (HUPO) World Congress 2015 in Vancouver (Canada). This effort was carried forward into an open podium discussion at the 5 th Symposium on Structural Proteomics in Halle/Saale (Germany) later that year.…”

“…A standard result file format should be developed and include a complete list of target and decoy identifications as potential true and known noise distributions. Integrative/hybrid modeling is tolerant to substantial error rates, and including the known noise (decoy matches) allows the modeling field to build ways to deal with noise in cross-linking data into their procedures (Berman et al, 2019;Rout and Sali, 2019). From a modeling perspective, such decoy matches represent an initial noise distribution that can be converted into a more accurate noise model by FDR estimation procedures.…”