Outcome of the First wwPDB Hybrid/Integrative Methods Task Force Workshop

Abstract

Summary Structures of biomolecular systems are increasingly computed by integrative modeling that relies on varied types of experimental data and theoretical information. We describe here the proceedings and conclusions from the first wwPDB Hybrid/Integrative Methods Task Force Workshop held at the European Bioinformatics Institute in Hinxton, UK, October 6 and 7, 2014. At the workshop, experts in various experimental fields of structural biology, experts in integrative modeling and visualization, and experts in data archiving addressed a series of questions central to the future of structural biology. How should integrative models be represented? How should the data and integrative models be validated? What data should be archived? How should the data and models be archived? What information should accompany the publication of integrative models?

Integrative structure and functional anatomy of a nuclear pore complex

“…Integrative structure determination of the S. cerevisiae NPC proceeded through four stages 97–100 (Extended Data Fig. 1; Supplementary Table 3; Supplementary Videos 1–3): (1) gathering data, (2) representing subunits and translating data into spatial restraints, (3) configurational sampling to produce an ensemble of structures that satisfies the restraints, and (4) analyzing and validating the ensemble structures and data (Supplementary Tables 2 to 4; Extended Data Figs.…”

“…We used the analysis and validation protocol published earlier 72,97 : Assessment began with a test of the thoroughness of structural sampling, followed by structural clustering of the modeled structures and estimating their precision based on the variability in the ensemble of good-scoring structures, quantification of the structure fit to the input information, and structure assessment by data not used to compute it; structure assessment by cross-validation was not performed in this case, because it takes ~10 weeks on approximately 2,500 cores to compute an ensemble of structures for a single set of input datasets. These validations are based on the nascent wwPDB effort on archival, validation, and dissemination of integrative structures 100 . We now discuss each one of these validations in turn.…”

The Cambridge Structural Database

“…We expect to see a continued push towards the federation of databases containing molecular structures (Sali et al, 2015) and the development of links between repositories. As these individual repositories grow, methods for searching them will also need to be improved.…”

Assembly and Molecular Architecture of the Phosphoinositide 3-Kinase p85α Homodimer

“…A "multistate model" is a model that specifies multiple discrete structural states of the system, all of which are required to explain the input information (19,(42)(43)(44). In contrast, in an ensemble of models, any single model explains the input information.…”