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The eBDIMS path-sampling server: generation, classification and interactive visualization of protein ensembles and transition pathways in 2D-motion space

2018-03-19

The recent rise of cryo-EM and X-ray high-throughput techniques is providing a wealth of new structures trapped in different conformations. Understanding how proteins transition between different conformers, and how they relate to each other in terms of function is not straightforward, and highly depends on the choice of the right set of degrees of freedom. Here we present eBDIMS server, an online tool and software for automatic classification of structural ensembles and reconstruction of transition pathways using coarse-grained (CG) simulations. The server generates CG-pathways between two protein conformations along with a representation in a simplified 2D-motion landscape based on the Principal Components (PCs) from experimental structures. For a conformationally rich ensemble, the PCs provide powerful reaction coordinates for automatic structure classification, detection of on-pathway intermediates and validation of in silico pathways. When the number of available structures is low or sampling is limited, Normal Modes (NMs) provide alternative motion axes for trajectory analysis. The path-generation eBDIMS method is available at a user-friendly website: https://login.biophysics.kth.se/eBDIMS/ or as standalone software. The server incorporates a powerful interactive graphical interface for simultaneous visualization of transition pathways in 2D-motion space and 3D-molecular graphics, which greatly facilitates the exploration of the relationships between different conformations.

📄 PDF Abstract BibTeX arXiv:1803.06873

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