Web-based visualization of 3D distance restraintsintegrated with NGL molecular graphics

Integrative/Hybrid approaches

Funding and acknowledgements

NGL library

CLMS distances in XI DEER distances in NGL Webapp

HIV-1 capsid at three scales216 hexameric and12 pentameric subunits,~2.4M unique atoms

Alexander S. Rose and Stephen K. BurleyRCSB Protein Data Bank

University of California San Diego and Rutgers, The State University of New Jersey

NGL library and viewer (https://github.com/arose/ngl)AS Rose & PW Hildebrand (2015)NGL Viewer: a web application for molecular visualization.Nucl. Acids Res. 43 (W1). doi:10.1093/nar/gkv402

Integrative/Hybrid approaches are increasingly being used to determinethree-dimensional (3D) structures of biological macromolecules by combininginformation from X-ray crystallography, NMR spectroscopy, and cryo-electronmicroscopy with data from diverse complementary experimental andcomputational methods. Two such complementary methods include cross-linking coupled mass spectrometry (CLMS) and double electron-electronresonance (DEER). These techniques can be used to generate distancerestraints that need to be visualized in the context of existing and modeledmacromolecular structures. At present, displaying distance restraints asannotations for structure modeling and validation is largely limited tospecialists. Herein, we utilize the web-based NGL library to provide 3Dvisualization of distance restraints integrated with general moleculargraphics.

Software availability

PDB ID 3J3Q

Application 1: Distances derived from chemical cross-linking coupledmass spectrometry (CLMS). Distance restraints between atoms can bedepicted with cylinders connecting one atom to the other. Above: CLMSdata for human serum albumin mapped onto PDB ID 1AO6 and renderedin 3D using the NGL library. Below: The same CLMS data for humanserum albumin shown in an arc diagram.The linked residue pair C476 toK564 is highlighted in both views, the 3D rendering and the 2D diagram.Both views are part of the integrated crosslink identification platform XI(https://github.com/Rappsilber-Laboratory/xi_installation)

Application 2: Distances derived from doubleelectron-electron resonance (DEER) experiments.Distance restraints for the inactive and active stateof bovine rhodopsin shown as probability densitydistributions (below) are rendered as volume slices(above) using the NGL library. Note how thedensity for residue 252 moves outwards in theactive state (orange arrow).

Acknowledgements DEER data: M Elgeti, Altenbach et. al.

(doi: 10.1073/pnas.0802515105)

XI: M Graham, C Combe, J Rappsilber CLMS data: A Belsom et. al.

(doi: 10.1074/mcp.M115.048504)

Scalable molecular graphics Library for biophysical/biochemical data WebGL-based, no plug-ins needed

Funding RCSB PDB is funded by a grant [DBI-

1338415; PI: SK Burley] from the NSF,the NIH, and the US DoE.

ALBU_HUMAN1 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460 480 500 520 540 560 585

Rendering of volumetricdata as isosurfaces at anydensity threshold or asvolume slices is available inthe NGL Webapp(http://arose.github.io/ngl/).Display of volume slicessupports linear and cubicinterpolation as well asfiltering by any densitythreshold.