PDB-Dev and Integrative/Hybrid (I/H) Modeling

PDB-Dev is a prototype deposition and archiving system for structural models obtained through integrative/hybrid (I/H) methods. Structures of complex macromolecular assemblies are difficult to obtain from a single structure determination method such as X-ray crystallography (X-ray), NMR spectroscopy (NMR) and Electron microscopy (3DEM). In such cases, a combination of complementary experimental and computational techniques are used to determine the structures. These methods are collectively called as integrative/hybrid (I/H) methods. In addition to X-ray crystallography, NMR, and 3DEM, methods such as small angle scattering (SAS), atomic force microscopy (AFM), chemical cross-linking (CX), co-purification, Förster resonance energy transfer (FRET), electron paramagnetic resonance (EPR), mass spectrometry (MS), H/D exchange (HDX), and various proteomics and bioinformatics techniques are part of I/H modeling methods. Spatial restraints derived from the different kinds of experimental and computational methods are combined to derive the structure of the macromolecular assembly. Integrative/hybrid (I/H) methods have been applied to determine the structures of assemblies such as the nuclear pore complex and its sub-complexes, the type III secretion system needle, the proteosomal lid sub-complex, the ESCRT-I complex, and an RNA ribosome-binding element from the turnip crinkle virus genome.

The I/H Methods Dictionary

We have developed a data dictionary for archiving structural models of macromolecular assemblies derived through integrative/hybrid methods. The I/H methods dictionary defines the data specifications required for archiving the I/H structural models, the associated spatial restraints and structural model computation protocols. This dictionary is a logical, modular extension of the PDBx/mmCIF dictionary currently used by the wwPDB for archiving atomic structures of macromolecules. The new dictionary extension addresses two fundamental requirements of I/H methods: (a) descriptions of spatial restraints derived from a variety of experimental techniques and (b) definitions of multi-scale, multi-state, and time-ordered ensembles of macromolecular assemblies. A general representation of multi-scale models together with the experimentally determined spatial restraints is an important feature of the new I/H methods dictionary.

The current I/H methods dictionary and associated documentation can be found here.

The I/H Methods Task Force

The wwPDB consortium has established an integrative/hybrid methods task force to tackle the many issues involved in archiving models determined by integrative/hybrid methods. This task force comprises of experts in the various experimental fields that contribute to the development of integrative/hybrid methods, along with experts in structural and computational biology, and experts in archiving. The PDB-Dev prototype system is developed based on the recommendations made by the wwPDB I/H methods task force published in a white paper (Sali et al., Structure. 2015 Jul 7; 23(7):1156-1167; doi:  10.1016/j.str.2015.05.013).

The Team

PDB-Dev and the I/H methods dictionary are being developed by a multi-disciplinary team of researchers and developers from the wwPDB and the I/H methods task force. The list of contributors can be found here.