Hybrid Biomolecular Modeling

Hybrid biomolecular models are obtained by combining simulation or prediction approaches (e.g., comparative modeling, structural bioinformatics, molecular dynamics simulation, normal mode analysis) with experimental approaches (e.g., nuclear magnetic resonance, X-ray crystallography, small-angle X-ray scattering, electron microscopy, X-ray free-electron lasers). Hybrid modeling of biomolecular structures and dynamics extends the capabilities of experimental techniques, by enriching structural information and facilitating dynamics studies of biomolecules. An example is fitting of structures of protein domains obtained by X-ray crystallography, nuclear magnetic resonance, or theoretical methods (structure prediction) into cryo-electron microcopy density maps of protein complexes. This allows obtaining the structure of complexes at atomic resolution when such resolution cannot be achieved using a single experimental technique, as is often the case with large and flexible complexes. Another example are hybrid modeling approaches that use normal mode analysis or molecular dynamics simulation to explore the conformational space of a model and obtain the conformation that best agrees with the experimental data from cryo-electron microscopy, small-angle X-ray scattering or X-ray free-electron lasers. On a different structural scale, mapping of known structures of macromolecular complexes onto density maps from cryo-electron tomography (visual proteomics) provides models of spatial relationships of different complexes in the context of cells and complements data from other proteomic approaches.

This Research Topic will cover both methodological developments and applications of hybrid modeling in the topical field of molecular biology. Also, it will provide a platform for discussion of current major challenges of hybrid modelling at different structural scales from atom to cell.