A virtual reality environment for interactive biomolecular drug discovery

Molecular simulation constitutes an indispensable tool in both understanding and designing biochemical archi-tectures.
Because it furnishes microscopic understanding into a wide range of diseases at the molecular scale, it ena-bles us to design
targeted pharmaceutical remedies to tackle disease at the nano-scale. Drug design problems are effectively problems of
'shape-matching' - i.e., designing a small molecular ligand (a drug) that fits snugly into a larger molecular receptor (a protein) -
a sort of "3d molecular Tetris". One of the biggest challenges in this design process arises from the fact that biomolecular
systems are flexible objects with thousands of degrees of freedom: there is a massive range of different shapes to consider
during drug design. To tackle this complexity, biomolecular scientists typically use the following approach: they assume that
biomolecules are rigid, and they use 'blind-search' algorithms to search the high-dimensional space of possible fits between
ligand and receptor.
Recent work at the frontiers of HCI and molecular simulation has begun to investigate another strategy to tackle this search
problem: interactive molecular simulation (iMS). The idea of iMS is that a well-designed human-computer interface offers the
opportunity for expert human intuition to 'guide' blind search algorithms, effectively combining the high-level reasoning abilities
of humans with the brute force compute power of modern HPC architec-tures. Initial results assessing the performance of iMS
tools have shown that they allow for much more efficient searching than 'blind-search' algorithms alone. Dr. David Glowacki's
group has been at the vanguard of iMS platform development, and has recently developed a prototype for a fully interactive
molecular simulation environment that works in the new class of emerging VR technologies, allowing for real-time 3d
manipulation of biomolecular dynam-ics simulations.
In this project, PhD candidate Helen Deeks will experiment with and develop this prototype iMS VR environment further, and
investigate how to transform it into an effective platform for designing drugs at the molecular nano-scale. The initial application
will focus on developing pharmaceutical remedies for malaria, a domain where Prof. Richard Sessions (Dept of Biochemistry)
has significant expertise and has offered his enthusiastic support. Specifi-cally, Helen's VR development activities will focus on
interactively designing drug molecules to inhibit the lactate dehydrogenase enzyme, which is key to killing the parasite
responsible for cerebral malaria. Successful execution of this project will benefit from expertise across a range of disciplines,
and thus has potentially wide impact across computer science, biochemistry, and health. This project will lead to outputs in
both the HCI research community and the biochemistry research community.