Immersive Examination of the Qualitative Structure of Biomolecules

The geometry of biomolecules dictates their function, but reasoning about that structure is difficult because of their 3D complexity and the range of scales involved. The wooden or plastic ball-and-stick models that are common in high-school chemistry labs help people reason about these issues when the molecules involved are small, but they are useless in the study of large biomolecules. Largely for this reason, 3D computer visualization tools have become essential in this field. However, these tools are limited by their interfaces. Traditional graphics workstations project a 3D model onto 2D screen, and interaction with the 3D model is indirect, using 2D mouse or pointing device. Immersive visualization is a potential solution to this: it allows a user to visualize a biomolecule in 3D and interact with it directly in 3-space. This paper reports upon a pilot study about the effects of immersive visualization upon an expert’s reasoning about the qualitative structure of these molecules. We ported a standard visualization application (PyMOL) to a CAVE-like immersive virtual environment (IVE), then invited three separate biochemistry research groups—people who use PyMOL routinely on desktop computers—to examine their favorite molecule in the IVE. Within ninety minutes of immersive investigation, each group reported a new discovery about the qualitative structure of that molecule. We believe that the immersive environment facilitated these discoveries by supporting and facilitating the natural spatial reasoning abilities of its users. An immersive virtual environment is a combination of hardware and software that provides a psychophysical experience of being surrounded by a computer-generated scene (see Figure 1). Immersive virtual environments provide users with an egocentric three-dimensional perspective: users are immersed in a virtual world, where they can explore complex spatial systems by looking through them, walking around them, and viewing them from different perspectives. Immersive environments may help people see and understand the structure of complex three-dimensional datasets; in contrast to more traditional graphics workstations, these environments allow one to visualize data using the well-practiced, non-concious analysis that automatically accompanies an embodied, egocentric visual perspective. There are several studies that have investigated the added value of immersive environments (Pausch, Proffitt, & Williams 1997; Ruddle, Payne, & Jones 1999; Arns, CruzNeira, & Cook 1999; Swan et al. 2003; Gruchalla 2004; Schulze et al. 2005; Demiralp et al. 2006). However, the results of these studies are mixed and the issue is somewhat controversial. There are few studies that clearly demonstrate the effectiveness of immersive environments for real-world problems, and none that approach this issue from the standpoint of qualitative reasoning. Our study does so, and our results indicate that experts understand more about the geometry of biomolecules if they use an immersive environment than if they use the same visualization tools on a standard desktop. Within ninety minutes of immersive investigation, each of the three groups in our study reported a new discovery about the qualitative structure of an important biomolecule—molecules that these groups had been studying for years in with the same software visualization tool on desktop environments. Immersive visualization has long been proposed as a means to analyze the complex three-dimensional structure of biological molecules (Ihlenfeldt 1997), and it is used by numerous investigators in basic research and industrial settings. Qualitative spatial analysis of the structure of these molecules at a range of scales is essential, because their overall three-dimensional configuration dictates the atomic interactions that are the basis of their function. Understanding the geometry of the building blocks of a biomolecule, and their relationships, is key to many of the grand-challenge problems in biochemistry: the rational design of drugs that enhance or inhibit molecular activity, the understanding of how steps in embryonic development normally proceed or go wrong in the presence of genetic mutations of molecular structure, and so on. This paper documents a pilot study in which three separate groups of biochemists visualized and interacted with individual biological molecules in a CAVE-like IVE. In each case, the immersive working session yielded new insights that the same biochemists had not previously achieved with their extensive use of the same visualization package on standard desktop computer displays. Large-scale spatial features, such as pockets and ridges, were readily identiFigure 1: A user interacting with a PyMOL visualization of a molecular surface inside a CAVE-like immersive virtual environment, which provides the opportunity to visualize the molecule using normal, everyday-world perceptual abilities that have been tuned and practiced from birth. fied when walking around the molecule displayed at human scale.