Immersive structural biology: A new approach to hybrid modeling of macromolecular assemblies

Abstract

Advanced biophysical imaging techniques, such as cryo-electron microscopy or tomography, enable 3D volumetric reconstructions of large macromolecular complexes in a near-native environment. However, pure volumetric data is insufficient for a detailed understanding of the underlying protein-protein interactions. This obstacle can be overcome by assembling an atomic model of the whole protein complex from known atomic structures, which are available from either X-ray crystallography or homology modeling. Due to many factors such as noise, conformational variability, experimental artifacts, and inexact model structures, existing automatic docking procedures are known to report false positives for a significant number of cases. The present paper focuses on a new technique to combine an offline exhaustive search algorithm with interactive visualization, collision detection, and haptic rendering. The resulting software system is highly immersive and allows the user to efficiently solve even difficult multi-resolution docking problems. Stereoscopic viewing, combined with head tracking and force feedback, generates an ideal virtual environment for true interaction with and solution of hybrid biomolecular modeling problems.