The University of Sheffield’s Krebs Institute Structural Biology Group, within the department of molecular biology and biotechnology, has recently installed an ActiveWall virtual reality (VR) system and Virtalis’ own VR software enabler for PyMOL, which enables molecular data to be visualized and interacted with in stereoscopic 3D. The Structural Biology Group’s focus is the atomic structure of biological macromolecules. By understanding these structures, they hope to elucidate the relationship between structure and function.
The proteins in cells are extremely tiny—typically just 2 to 10 nm across. Yet, each protein molecule comprises between 1,500 and 20,000 individual atoms. Patrick Baker is a researcher in protein crystallography within the group. “Studying such complex structures can be mind boggling at times and, historically, we needed large polystyrene or wooden models to represent the structures. Twenty years ago, it took between one and five years to determine a structure. Now, we can have that structure within a week of creating the crystal. Structural biologists have long been at the forefront of what computers can do, owing to the enormous demands placed on them by molecular graphics. The advent of stereoscopic 3D viewing has been a further leap forward, because we can see so much more of the structure without becoming confused.”
The Virtalis ActiveWall is an immersive, interactive 3D visualization system. ActiveWall draws on active stereo technology and features a custom screen, specialist computer, Virtalis custom software, and powerful projectors. Movements within the ActiveWall environment are tracked using a tracking system. This added functionality alters the perspective of the visuals according to the user’s position and orientation within the scene to give a natural and accurate sense of relationship and scale. The hand-held controller enhances the immersive experience. The user can navigate through the virtual world, pick and manipulate component parts in real-time, and make decisions on the fly. Through work conducted for the University of Arkansas, Virtalis developed a VR software enabler for PyMOL.
“We’re working with chemists to design molecules that can bind to, and inhibit, essential proteins in bacteria as leads to new anti-infectious agents to combat increasing drug resistance. We collaborate with pharmaceutical companies on understanding the relationship between structure and function as we move towards personalized medicine. Once we start looking at such interactions there is another leap in complexity and we really need that third dimension.”
One of the projects the Structural Biology Group is using its Virtalis ActiveWall and the PyMOL 3D/VR-enabler for is to analyze proteins from the bacteria Burkholderia pseudomalleii, a soil-borne organism that is the causative agent of the tropical disease melliodosis. Working with colleagues in Thai, Malaysian, and Singaporean universities, the Group is investigating proteins with an unknown function. They discovered that one, Burkholderia lethal factor 1 (BLF1), has a very similar 3D shape to the cytotoxic necrotizing factor of Escherichia coli, indicating that it, too, is a potent toxin. It transpired that although both these toxins shared the same mechanism, their cellular targets were different. BLF1 targets protein translation, killing the host cell. Understanding the molecular structure and function of this toxin may lead to ways to counter pathogenicity and ameliorate the symptoms of the disease. Additionally, the toxic effect of this protein could perhaps be harnessed as a drug to kill rapidly dividing cells, as found in many cancers.