KinImmerse: Macromolecular VR for NMR ensembles

Abstract

Background: In molecular applications, virtual reality (VR) and immersive virtual environments have generally been used and valued for the visual and interactive experience - to enhance intuition and communicate excitement - rather than as part of the actual research process. In contrast, this work develops a software infrastructure for research use and illustrates such use on a specific case.

Methods: The Syzygy open-source toolkit for VR software was used to write the KinImmerse program, which translates the molecular capabilities of the kinemage graphics format into software for display and manipulation in the DiVE (Duke immersive Virtual Environment) or other VR system. KinImmerse is supported by the flexible display construction and editing features in the KiNG kinemage viewer and it implements new forms of user interaction in the DiVE.

Results: In addition to molecular visualizations and navigation, KinImmerse provides a set of research tools for manipulation, identification, co-centering of multiple models, free-form 3D annotation, and output of results. The molecular research test case analyzes the local neighborhood around an individual atom within an ensemble of nuclear magnetic resonance (NMR) models, enabling immersive visual comparison of the local conformation with the local NMR experimental data, including target curves for residual dipolar couplings (RDCs).

Conclusion: The promise of KinImmerse for production-level molecular research in the DiVE is shown by the locally co-centered RDC visualization developed there, which gave new insights now being pursued in wider data analysis.

Figure 1

The DiVE. Schematic showing the physical configuration of the 6-sided Duke immersive Virtual Environment (DiVE), operated by the Visualization Technology Group . The sliding-door front wall is open, and two of the large stand mirrors are shown that direct images from the projectors onto the translucent walls; a sixth projector is beneath the floor.

Figure 2

Flow chart of the KinImmerse logic. Diagram illustrating the flow of steps in a cycle of the callback-style API for 6-sided display and interactive navigation. Steps in boxes with bold borders are custom written for KinImmerse, while the rest are provided by the Syzygy toolkit.

Figure 3

NOEs for Ile3 Hβ of 1D3Z, in KiNG vs KinImmerse user session. a) Traditional display of the 10-model 1D3Z ubiquitin ensemble [42] in KiNG, with backbone in white and sidechains cyan. For model 1, the Hβ of Ile3 is highlighted with a brown ball and NOE measurements between it and neighboring atoms are shown as dotted lines. b) Working KinImmerse session in the DiVE, for those same NOEs (dashed lines). All models were co-centered on Ile3 Hβ (gray ball), but only model 1 is shown here for clarity on the flat page; bonds to H atoms are in orange for emphasis. The user has drawn a 3D annotation to indicate that the distances to the two Hβs of Ser65 appear to be reversed. Photographed in the DiVE by JNB, VBC, and DCR.

Figure 4

NH RDC curves, co-centered on the N atom. An example of RDC target curves (in green) calculated by RDCvis and shown in KinImmerse: backbone NH of Asp38 in 1D3Z, for all 10 models of the ensemble. Co-centered in the DiVE, saved as an output kinemage, and then displayed in KiNG.

Figure 5

Evaluating two clusters of loop models by RDC geometry. Helix-helix loop 36–40 in the 1Q2N Z-domain ensemble [43] shows two quite different conformational clusters of models, in spite of the fact that all 10 models match the experimental RDC data that measures orientation. a) Pro38 CαH bond vectors for the two model clusters point in nearly opposite directions, matching opposite limbs of the paired RDC target curves. b) Quality comparison of the two model clusters, from the MolProbity structure-validation site [34]: the 4 bad models have Ramachandran outliers (green), many steric clashes (hot pink spikes) and sidechain rotamer outliers (gold), while the 6 good models have no clashes or Ramachandran outliers, few bad rotamers, and several hydrogen bonds (lenses of green dots). One can conclude that the RDC match for the 4-model conformation is a coincidence, and those models are incorrect.

Figure 6

High school students experiencing a molecule in the DiVE. Students in the Howard Hughes phage-hunters summer program locating structural features of a DNA double helix in the DiVE. These demo sessions used the VirTools prototype of the VR kinemage display system (see Methods). Photography by Chris Hildreth, Director of Duke University Photography.