The ability for scientists across the world to work together toward a common goal has been significantly bolstered by the advent of computer technology and the internet. Researchers can now take their questions and ideas from the lab to the web, where many minds can collaborate to provide fresh insight, and build upon models and data available to them on their screen.
But what about bringing the web into the lab? What if dozens or hundreds of researchers could lose the screen and converge to one place to view, discuss and manipulate a molecule in real time -- without the need to hop on a plane or even use a computer mouse?
Many scientists are already doing this with the use of virtual reality (VR). Previously thought of as mainly tools for gaming and entertainment, VR headsets and environments are making their way into laboratories as platforms for scientific cooperation in areas such as drug discovery and food science. VR is unique in that it can provide the natural hands-on feeling of working at a bench while allowing for real-time communication and three-dimensional interactions with models normally viewed through a two-dimensional screen.
Steve McCloskey and Keita Funakawa, co-founders of the science-focused VR platform Nanome, see the 3D virtual environment as an ideal “home” for global collaboration between researchers. During a time when meeting face to face and traveling to different labs and locations has become more difficult, VR has been making strides in facilitating cooperative research, including into SARS-CoV-2.
“The international collaboration speed has increased by orders of magnitude by enabling scientists to meet from anywhere in the world instantaneously and pull up the latest molecular data to discuss in real time,” said McCloskey.
A Hands-on Approach to Real-time Collaboration
The process of developing a concept into a functioning solution, such as a new drug or energy source, cannot be done alone and benefits from idea-sharing and feedback from a diverse group of minds. As Funakawa puts it, “Science shouldn’t be siloed.”
In virtual reality, collaborators have the opportunity to look at a model in the same space at the same time and demonstrate their ideas in a 3D environment as though they were standing in the same room with their colleagues. VR also has the ability to bring to life a model a scientist may have in their head with fewer limitations than traditional mouse-clicking and cursor-dragging on a computer screen.
Natural hand motions can be used to build, modify, rotate and size up or size down a 3D molecule model, and researchers can walk around or even step inside of the molecule in a way that differs from the fixed perspective of looking at a computer screen. This flexibility to look at the model from any perspective through natural head, body and hand motions can lead scientists to notice details that may not have been as apparent when viewed another way or imagined in their own mind.
“One could look at some 2D images of molecules on a 2D screen, but there are significant bottlenecks that are not conducive to understanding 3D content,” said McCloskey. “Fundamentally, science and molecules are in 3D. Why limit design creativity and analysis to a 2D screen? Users literally using their fingers to reach in and highlight points of interest in 3D are just things that cannot be done in 2D.”
As with any new technology being introduced into the lab space, there are questions and concerns about costs, training, and the hardware and materials needed to get the system up and running. While acknowledging that the implementation of VR in this environment has not been without its challenges, the Nanome team said they have seen accelerated advancement along the adoption curve, with many enthusiastic early adopters, including in the biopharmaceutical space.
“There have been attempts to use 3D interfaces for analyzing molecular structures for decades and many people have dreamt of the day where the technology could enable them to reach out and hold their molecules in their hands,” McCloskey explained. “Many attempts were premature or cost-prohibitive until the VR gaming industry was able to catapult VR out of obscurity and into the mainstream. We’ve put together a platform that they have been dreaming about, so naturally those early adopters have been very excited to see science fiction become reality. Almost everyone says they wish they had VR when they were in school taking organic chemistry classes.”
The team said the now relatively affordable and accessible hardware requirements for getting started in VR have been a driver of the accelerated acceptance and adoption among laboratory scientists. Most VR headsets and controllers can be used with a typical workstation computer, although the recent emergence of wireless, standalone headsets offer increased flexibility and mobility. For example, the Nanome software can be used with the consumer-grade wireless Oculus Quest headset. As far as training, the Nanome team said it may take users as little as 30 minutes to an hour to get acquainted with the platform’s controls and tools, as tasks are completed with simple hand motions everyone is used to, like pointing, pinching and grabbing.
A Meeting of Minds and Molecules
VR has already been used for a wide variety of research endeavors in areas such as medicinal chemistry, structural biology and protein engineering, and has served as the birthplace of many promising designs and discoveries over the last few years. Researchers have used Nanome to identify and rule out potential drug targets, as well as build and refine new drug candidates using the platform’s interactive 3D modeling capabilities.
For example, UC San Diego researcher Zoran Radić, while investigating the interaction between a deadly nerve agent called A-232 and the vital enzyme AChE in virtual reality, discovered a key difference in how A-232 binds to AChE compared with other nerve agents for which oxime compounds have been used as an antidote. This discovery bolstered further work by Radić and his colleagues to identify alternative antidotes, and the team designed seven new candidates while continuing to use Nanome to help analyze their designs.
Central to the platform’s ability to aid in drug discovery and chemical engineering is the incorporated computational simulation of molecular dynamics. More than just a place to view static molecular structures in 3D, the VR environment can be compared to the inside of a test tube or petri dish, where components will interact realistically when coming in contact with each other. Through automated docking and the ability to view molecular dynamics simulations from the inside of a zoomed-in macromolecule or supramolecular structure, researchers can gain a new perspective on the pathogenesis of a virus or viability of a possible drug candidate.
In a case study published by Oculus for Business last year, Lewis Whitehead, a medicinal chemist for biotechnology company Nimbus Therapeutics, said the new perspective offered by VR saves time and costs by accelerating the building, sharing and analysis of small molecule drug candidates in silico. For example, Whitehead viewed the dynamics of the AMPKβ2 enzyme, which is a therapeutic target for metabolic diseases, in Nanome and realized that a strategy his team had developed for improved drug selectivity would not work in the way they had imagined prior to seeing the simulation in VR. Rather than spend more time on an ultimately viable strategy, Whitehead and his team were able to refocus on a more promising strategy, using VR to share their ideas and findings with one another rather than a simple slide presentation.
“After enough rotating on a flat monitor, there is somewhat of a model that some scientists can build in their head, but that model is imperfect compared to looking at the real molecular data in VR, which doesn’t lose fidelity when stored in human memory,” McCloskey explained. “Furthermore, a model in a scientist’s head stays there and can’t easily be shared with their team. VR helps get everyone on the same page by putting the real molecular data right in front of a team of scientists that can point to and discuss exact areas of interest.”
Facing COVID-19 on the Virtual Battleground
Collaboration in the virtual world can aid discovery in the context of colleagues from the same organization working together on a project, and it can also occur on a global scale, bringing together international collaborators to tackle the most harrowing problems threatening health and safety around the world. Enter COVID-19.
Investigations into the SARS-CoV-2 virus, its proteins and their interactions with human enzymes began as early as February 2020, when scientists from Australia and the United States used Nanome to attempt to better understand the structure of the virus’ spike protein. The researchers were able to view the published protein structure determined by another research team through cryo-EM, highlight the gaps in the structure where specific amino acid residues had not yet been determined, and compare the published model to a model one of the researchers had designed himself. They were also able to compare the SARS spike protein to that of SARS-CoV-2, zooming in to specific hydrogen bond interactions that give insight into why the latter is so much more virulent, and view the simulated interaction between the ACE2 receptor and the protein.
As COVID-19 research progressed, Funakawa said the VR platform became a tool for the “boots on the ground” attempting to answer questions about the virus, identify drug targets, build and analyze drug candidates and better understand different virus mutations and variants. It also became a virtual meeting place for scientists around the world to present their own ideas, models and findings.
In May 2020, Nanome co-authored a paper with Hong Kong-based AI company Insilico Medicine describing 10 potential small molecule inhibitors that would target the main protease of SARS-CoV-2. These potential drug candidates were created by refining AI-generated molecules within the VR platform. In June 2020, Nanome joined Exscalate4Cov, a European Union Commission-sponsored supercomputing project aimed at screening chemical libraries of billions of molecules for potential COVID-19 drug candidates.
The Nanome team also discussed the creativity they have seen among users in their approaches to molecular modeling and analysis. One example of this is a project by a PhD student who tested how components of essential oils such as lavender would interact with the binding sites of SARS-CoV-2 proteins. Another PhD student joined the Nanome team as a guest speaker on their YouTube page to discuss research into the binding of LSD with human serotonin receptors. The group demonstrated these interactions in VR and spoke about the therapeutic potential of psychedelic drugs in the treatment of mental illness — another public health crisis that has been exacerbated by the pandemic.
Whether discussing viral spike proteins or hallucinogens, collaborators in the VR space can use a virtual whiteboard to take notes and draw diagrams, and view research papers and other documents on virtual screens, in conjunction viewing the simulated models and interactions.
The Lab of the Future
McCloskey and Funakawa emphasize that the use of VR for scientific endeavors is not a far-off concept — it is happening now and only has room to grow. VR companies like Oculus, HTC and Valve are working to develop more powerful and flexible VR systems that software like Nanome can leverage for further efficiency and advanced capabilities. VR is being used in conjunction with AI, as shown in the study of AI-generated drug candidates, and being paired with extensive chemical libraries and powerful supercomputers, such as in the Excalate4Cov project, to expand the possibilities of what researchers can achieve in this virtual molecular sandbox.
“The lab of the future that we’re already seeing emerge includes scientists located anywhere in the world directing their research through virtual reality, while automated lab tools do the busywork of synthesizing chemicals and testing. This future lab can even be distributed around the world depending on what needs to be done and when,” McCloskey concluded. “More and more components of the physical lab are being automated or outsourced, leaving scientists with a larger obligation to be creative directors, spinning up AI programs where needed, analyzing results from experiments and computations collaboratively, and planning their next course of action they can send back to their robot lab or CRO.”