Viewing and sharing molecular dynamics simulations on the web using the MDsrv
Creators: name: Tiemann, Johanna K. S.
name: Guixà-González, Ramon
name: Rose, Alexander S.
name: Hildebrand, Peter W.
Publisher: name: F1000 Research Limited
Year: 2019

description: Molecular dynamics (MD) simulations are these days a well-established and widely used technique to investigate time-resolved motions of macromolecules such as G protein-coupled receptors (GPCR). Sharing of the resulting coordinate trajectories for visualization is complicated by their size, the requirement of having special software set-up and the knowledge of the software usage. However, in light of increasingly interdisciplinary research and remote collaborations, it is desirable to make sharing of MD trajectories easier to facilitate discussions and further analyses. In contribution, we present MDsrv [1], a tool to serve trajectories of molecular coordinates and visualize them in a web browser by employing the NGL Viewer [2]. It supports structures, topologies, and trajectories from common MD packages including Amber, Gromacs, NAMD, Tinker or Desmond. For interactive viewing of the MD simulations by co-workers or colleagues all over the world only a web browser is needed and no installation of any MD-specific software is required. MDsrv is available as a software package (via PyPi and conda), to be run locally or deployed to a dedicated web-server to make data from MD simulations accessible to a wide audience of researchers and students.<br>By providing access via the web, the MDsrv bridges the gap between computational and experimental researchers and even promotes concepts for publishing MD data along with publications of their analysis. The concept of visualizing and sharing of MD trajectories via the web can be considered as a major step of the MD field towards a community following the FAIR (Findable, Accessible, Interoperable, Re-usable) principles [3]. This process will be significantly guided by the usage of visual sharing tools like the MDsrv.<br>In our laboratory, the MDsrv is implemented to share and distribute dynamic facets of G protein-coupled receptors (GPCRs), one of the pharmacologically most important receptor class. We present examples from current GPCR projects, where structural flexibility is explicitly important for function, such as the investigation of the selective binding pathway of non-peptide antagonist MCL0129 to human melanocortin-4 receptor(MC4R) [4], and receptor coupling specificity [5] (for further examples see http://nglviewer.org/mdsrv).<br><br>References:<br>[1] Tiemann, J. K. S., Guixà-González, R., Hildebrand, P. W., &amp; Rose, A. S. (2017). MDsrv: Viewing and sharing molecular dynamics simulations on the web. Nature Methods, 14(12), 1123–1124. https://doi.org/10.1038/nmeth.4497<br>[2] Rose, A. S., &amp; Hildebrand, P. W. (2015). NGL Viewer: a web application for molecular visualization. Nucleic Acids Research, 43(W1), W576–W579. https://doi.org/10.1093/nar/gkv402<br>[3] Wilkinson, M. D., Dumontier, M., Aalbersberg, Ij. J., Appleton, G., Axton, M., Baak, A., … Mons, B. (2016). The FAIR Guiding Principles for scientific data management and stewardship. Scientific Data, 3, 160018. Retrieved from http://dx.doi.org/10.1038/sdata.2016.18<br>[4] Saleh, N., Kleinau, G., Heyder, N., Clark, T., Hildebrand, P. W., &amp; Scheerer, P. (2018). Binding, Thermodynamics, and Selectivity of a Non-peptide Antagonist to the Melanocortin-4 Receptor. Frontiers in Pharmacology, 9(JUN), 560. https://doi.org/10.3389/fphar.2018.00560<br>[5] Rose, A. S., Elgeti, M., Zachariae, U., Grubmüller, H., Hofmann, K. P., Scheerer, P., &amp; Hildebrand, P. W. (2014). Position of Transmembrane Helix 6 Determines Receptor G Protein Coupling Specificity. Journal of the American Chemical Society, 136(32), 11244–11247. https://doi.org/10.1021/ja5055109